What are some good books on oncology?

What are some good books on oncology?

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I'm looking for some book suggestions on oncology, preferably I want them to be fairly recent. I am not worried if they are fairly technical, as long as they have good accurate content and layout.

You could try DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. It has detailed information on both biological and clinical aspects of cancer. Apparently, the publishers regularly release online updates to cover the latest developments in oncology.

Reference to the current edition:

DeVita VT, Rosenberg SA, Lawrence TS, editors. DeVita, Hellman, and Rosenberg's cancer: principles & practice of oncology. 11th Edition. Philadelphia: Wolters Kluwer; 2018. 2432 p.

The must-have textbook: The Biology of Cancer from Robert Weinberg

The Second Edition was published in 2013, I didn't heard about a newer Edition yet but the current one is well recognized in the field

50 Books to Read if You Love Medicine

I wasn&rsquot always a writer. As a preteen, I wanted to be a pediatric oncologist, a dream that continues today. My love of medicine and people propelled me toward psychology, then public health, where I could combine everything into fields like psychosocial oncology and perinatal psychology. My not-so-secret desire to be a doctor, though, has never really gone away. At this point, I have accepted that my graduate school loans are sizable enough, and my life no longer has room for the possibility of ever going to medical school &ndash and besides, when I did take some prerequisites, although I love reading medical textbooks, my brain just does not like rote memorization&hellipwhich is a problem in the biological sciences. But I still love reading about medicine, doctoring, and anything in the medical field in medical books.

Here, in no particular order, are 50 must-read and best medical books. I like to think that if you devour reruns of ER and House, that you&rsquoll like these, too. They&rsquore mostly books about medicine that are nonfiction, with fiction marked with a (*) and forthcoming books marked (**).

    When Breath Becomes Airby Paul Kalanithi.One of my favorites. &ldquoAt the age of thirty-six, on the verge of completing a decade&rsquos worth of training as a neurosurgeon, Paul Kalanithi was diagnosed with stage IV lung cancer. One day he was a doctor treating the dying, and the next he was a patient struggling to live. And just like that, the future he and his wife had imagined evaporated.&rdquo

  1. The Spirit Catches You and You Fall Down by Anne Fadiman. &ldquoThe Spirit Catches You and You Fall Down explores the clash between a small county hospital in California and a refugee family from Laos over the care of Lia Lee, a Hmong child diagnosed with severe epilepsy. Lia&rsquos parents and her doctors both wanted what was best for Lia, but the lack of understanding between them led to tragedy.&rdquo
  2. Wit* by Margaret Edson. &ldquoMargaret Edson&rsquos powerfully imagined Pulitzer Prize&ndashwinning play examines what makes life worth living through her exploration of one of existence&rsquos unifying experiences―mortality―while she also probes the vital importance of human relationships. What we as her audience take away from this remarkable drama is a keener sense that, while death is real and unavoidable, our lives are ours to cherish or throw away―a lesson that can be both uplifting and redemptive.&rdquo
  3. Letters to a Young Doctor by Richard Selzer. &ldquoHighly candid, insightful, and unexpectedly humorous essays on both the brutality and the beauty of the profession in which saving and losing lives is all in a day&rsquos work. A timeless collection by the &ldquobest of the writing surgeons&rdquo (Chicago Tribune).&rdquo
  4. The Lives of a Cell: Notes of a Biology Watcher by Lewis Thomas. &ldquoElegant, suggestive, and clarifying, Lewis Thomas&rsquos profoundly humane vision explores the world around us and examines the complex interdependence of all things. Extending beyond the usual limitations of biological science and into a vast and wondrous world of hidden relationships, this provocative book explores in personal, poetic essays to topics such as computers, germs, language, music, death, insects, and medicine.&rdquo
  1. The Man Who Mistook His Wife for a Hat by Oliver Sacks. A classic in the field of neurology. If you read one book by Sacks, make it this one.
  2. The Illness Narratives: Suffering, Healing, and the Human Condition by Arthur Kleinman. &ldquoBased on twenty years of clinical experience studying and treating chronic illness, a Harvard psychiatrist and anthropologist argues that diagnosing illness is an art tragically neglected by modern medical training, and presents a compelling case for bridging the gap between patient and doctor.&rdquo
  3. The Human Side of Cancer: Living With Hope, Coping With Uncertainty by Jimmie Holland. This book was my bible when I worked in psycho-oncology. Dr. Holland is the founder of the field, and she&rsquos just brilliant.
  4. When the Air Hits Your Brain: Tales from Neurosurgery by Frank Vertosick, Jr. &ldquoWith poignant insight and humor, Frank Vertosick Jr., MD, describes some of the greatest challenges of his career, including a six-week-old infant with a tumor in her brain, a young man struck down in his prime by paraplegia, and a minister with a .22-caliber bullet lodged in his skull. Told through intimate portraits of Vertosick&rsquos patients and unsparing yet fascinatingly detailed descriptions of surgical procedures, When the Air Hits Your Brain―the culmination of decades spent struggling to learn an unforgiving craft―illuminates both the mysteries of the mind and the realities of the operating room.&rdquo
  5. Dying Well: Peace and Possibilities at the End of Life by Ira Byock. &ldquoThrough the true stories of patients, he shows us that a lot of important emotional work can be accomplished in the final months, weeks, and even days of life. It is a companion for families, showing them how to deal with doctors, how to talk to loved ones&mdashand how to make the end of life as meaningful and enriching as the beginning.&rdquo
  6. A Stitch of Time: The Year a Brain Injury Changed My Language and Life by Lauren Marks. &ldquoLauren Marks was twenty-seven, touring a show in Scotland with her friends, when an aneurysm ruptured in her brain and left her fighting for her life. She woke up in a hospital soon after with serious deficiencies to her reading, speaking, and writing abilities, and an unfamiliar diagnosis: aphasia. This would be shocking news for anyone, but Lauren was a voracious reader, an actress, director, and dramaturg, and at the time of the event, pursuing her PhD. At any other period of her life, this diagnosis would have been a devastating blow. But she woke up&hellipdifferent.&rdquo
  7. The Gene: An Intimate History by Siddhartha Mukherjee. &ldquo&hellipIn this biography Mukherjee brings to life the quest to understand human heredity and its surprising influence on our lives, personalities, identities, fates, and choices.&rdquo
  8. How We Do Harm: A Doctor Breaks Ranks About Being Sick in America by Otis Webb Brawley. &ldquo&hellipexposes the underbelly of healthcare today―the overtreatment of the rich, the under treatment of the poor, the financial conflicts of interest that determine the care that physicians provide, insurance companies that don&rsquot demand the best (or even the least expensive) care, and pharmaceutical companies concerned with selling drugs, regardless of whether they improve health or do harm.&rdquo
  9. Blue Collar, Blue Scrubs: The Making of a Surgeon by Michael Collins. &ldquo&helliptaking readers from his days as a construction worker to his entry into medical school, expertly infusing his journey to become a doctor with humanity, compassion, and humor. From the first time he delivers a baby to being surrounded by death and pain on a daily basis, Collins compellingly writes about how medicine makes him confront, in a very deep and personal way, the nature of God and suffering―and how delicate life can be.&rdquo
  10. I Knew A Woman: Four Women Patients and Their Female Caregiver by Cortney Davis. &ldquoA poet and nurse-practitioner with twenty five years&rsquo experience, Davis reveals the beauty of the body&rsquos workings by unfolding the lives of four patients who struggle with its natural cycles and unexpected surprises: pregnancy and childbirth, illness and recovery, sexual dysfunction and sexual joy. An abundance of solid medical information imbues every graceful line.&rdquo
  11. Mountains Beyond Mountains by Tracey Kidder. &ldquoIn medical school, Paul Farmer found his life&rsquos calling: to cure infectious diseases and to bring the lifesaving tools of modern medicine to those who need them most. Kidder&rsquos magnificent account takes us from Harvard to Haiti, Peru, Cuba, and Russia as Farmer changes minds and practices through his dedication to the philosophy that &ldquothe only real nation is humanity.&rdquo At the heart of this book is the example of a life based on hope and on an understanding of the truth of the Haitian proverb &ldquoBeyond mountains there are mountains&rdquo&ndashas you solve one problem, another problem presents itself, and so you go on and try to solve that one too.&rdquo
  12. What Doctors Feel: How Emotions Affect the Practice of Medicine by Danielle Ofri. &ldquoHow do the stresses of medical life&mdashfrom paperwork to grueling hours to lawsuits to facing death&mdashaffect the medical care that doctors can offer their patients? Digging deep into the lives of doctors, Ofri examines the daunting range of emotions&mdashshame, anger, empathy, frustration, hope, pride, occasionally despair, and sometimes even love&mdashthat permeate the contemporary doctor-patient connection.&rdquo
  13. God&rsquos Hotel: A Doctor, a Hospital, and a Pilgrimage to the Heart of Medicine by Victoria Sweet. &ldquoSan Francisco&rsquos Laguna Honda Hospital is the last almshouse in the country, a descendant of the Hôtel-Dieu (God&rsquos hotel) that cared for the sick in the Middle Ages. Ballet dancers and rock musicians, professors and thieves&mdash&ldquoanyone who had fallen, or, often, leapt, onto hard times&rdquo and needed extended medical care&mdashended up here. So did Victoria Sweet, who came for two months and stayed for twenty years.&rdquo
  14. This Won&rsquot Hurt a Bit (And Other White Lies): My Education in Medicine and Motherhood by Michelle Au. &ldquoIt&rsquos a no-holds-barred account of what a modern medical education feels like, from the grim to the ridiculous, from the heartwarming to the obscene. Unlike most medical memoirs, however, this one details the author&rsquos struggles to maintain a life outside of the hospital, in the small amount of free time she had to live it. And, after she and her husband have a baby early in both their medical residencies, Au explores the demands of being a parent with those of a physician, two all-consuming jobs in which the lives of others are very literally in her hands.&rdquo
  15. Black Man in a White Coat: A Doctor&rsquos Reflections on Race and Medicine by Damon Tweedy. &ldquo&hellipexamines the complex ways in which both black doctors and patients must navigate the difficult and often contradictory terrain of race and medicine. As Tweedy transforms from student to practicing physician, he discovers how often race influences his encounters with patients. Through their stories, he illustrates the complex social, cultural, and economic factors at the root of many health problems in the black community. These issues take on greater meaning when Tweedy is himself diagnosed with a chronic disease far more common among black people. In this powerful, moving, and deeply empathic book, Tweedy explores the challenges confronting black doctors, and the disproportionate health burdens faced by black patients, ultimately seeking a way forward to better treatment and more compassionate care.&rdquo
  16. Five Days at Memorial: Life and Death in a Storm-Ravaged Hospital by Sheri Fink. &ldquoAfter Katrina struck and the floodwaters rose, the power failed, and the heat climbed, exhausted caregivers chose to designate certain patients last for rescue. Months later, several of those caregivers faced criminal allegations that they deliberately injected numerous patients with drugs to hasten their deaths. Five Days at Memorial, the culmination of six years of reporting, unspools the mystery of what happened in those days, bringing the reader into a hospital fighting for its life and into a conversation about the most terrifying form of health care rationing.&rdquo
  17. Critical Care: A New Nurse Faces Death, Life, and Everything in Between by Theresa Brown. &ldquo&hellipthe powerful and absorbing memoir of Theresa Brown&mdasha regular contributor to the New York Times blog &ldquoWell&rdquo&mdashabout her experiences during the first year on the job as an oncology nurse in the process, Brown sheds brilliant light on issues of mortality and meaning in our lives.&rdquo
  18. The Cancer Journals by Audre Lorde. &ldquoLiterary Nonfiction. Memoir. African American Studies. LGBT Studies. Moving between journal entry, memoir, and exposition, Audre Lorde fuses the personal and political as she reflects on her experience coping with breast cancer and a radical mastectomy.&rdquo

What do you think are the best medical books? Want to learn even more about the subject? Check out &ldquo100 Must-Read Books About The History of Medicine.&rdquo

Cancer Biology

A thorough yet concise account of cancer biology, this book emphasises the cellular and molecular mechanisms involved in the transformation of normal into malignant cells, the invasiveness of cancer cells into host tissues, and the metastatic spread of cancer cells in the host organism. It also defines the fundamental pathophysiological changes that occur in tumour tissue and in the host animal or patient. The approach throughout the book is to discuss the historical development of a field, citing the key experimental advances to the present day, and to evaluate the current evidence that best supports or rules out concepts of the molecular and cellular mechanisms regulating cancer cell behaviour. For all the areas of fundamental cancer research, an effort has been made to relate basic research findings to the clinical disease states. The book is well illustrated with schematic diagrams and actual research data to demonstrate points made in the text, and there is an extensive, up-to-date bibliography.

Twelve Of The Best Books About Biology Of 2018

Biology is comprised of a vast number of fields of study, not the least of which are evolution, genetics and natural history, which are my main focus in this collection. I ended up with 12 books in this group, all of which explore important biological concepts, ranging from how artificial selection has affected the evolution of domesticated animals, how urban environments have created a unique environment that is altering the evolution of birds and other wildlife, the evolution of modern humans, what caused the extinction of most of the world’s megafauna, the amazing variety of scientific model systems that are teaching us so much about ourselves and about the natural world, how plants create flowers, and several books that celebrate the rich biodiversity of trees, of bees, and of fishes. I hope you enjoy these books as much as I have enjoyed finding and sharing them with you.

Unnatural Selection by Katrina van Grouw (Princeton University Press, 2018 Amazon US / Amazon UK)

This oversized book features exquisitely detailed drawings of skulls, skeletons, feathers, claws and more, all of which illustrate how domestic animals changed rapidly, thanks to artificial selection by animal breeders. The author of this gorgeous book, a scientist herself, argues that scientists have long overlooked the most convincing demonstrations of evolution in action by ignoring how humans have shaped the evolution and anatomy of domesticated animal breeds throughout the centuries, as her illustrations clearly show. Even if you never read a word of this well-written book (which would be a shame because the prose is excellent), the lovely drawings alone make it absolutely essential for anyone who is interested in animals, whether it is a general interest, or a more specific leaning towards animal anatomy and/or evolutionary biology. You don’t need to be a scientist, veterinarian, scientific illustrator or artist to fall deeply, madly in love with this painstakingly accurate, stunning book, so if you are buying this as a gift, be sure to pick up a copy for yourself, too.

Darwin Comes to Town: How the Urban Jungle Drives Evolution by Professor Menno Schilthuizen (Quercus Books, 2018: Amazon US / Amazon UK)

Humans have (and still are) changing plants and animals to suit our needs through selective breeding, but many wild birds and animals are now moving into cities, and are being changed by this decision so they can live amongst us more successfully. In fact, urban evolution has been occurring in our cities for centuries, under our noses, but we have only recently become aware of this. This interesting and wonderfully readable book discusses the extraordinary power of natural selection and how it’s driving evolution amongst urban wildlife, which are becoming ever more specialized to live in this unique habitat. The author includes persuasive examples of urban evolution in action, such as “city adapted” songbirds whose songs, calls, plumage colors, nesting behaviors and even peak activity times differ from their rural cousins so they can prosper in a more toxic, noisier, brighter, and busier environment than the wild spaces that their ancestors once knew. The writing is clear, the concepts are easily understood, and the examples include many familiar animals. This thoughtful and thought-provoking book will have broad appeal, but will be particularly enlightening for those who wish to learn more about how birds and wildlife are adapting to the modern urban ecosystem.

First in Fly: Drosophila Research and Biological Discovery by Stephanie Eliza Mohr (Harvard University Press, 2018: Amazon US / Amazon UK)

For more than 100 years, laboratory investigations into fruit flies, Drosophila melanogaster, have revealed that these tiny insects’ genes, gene networks, cell interactions, physiology, immunity, and behaviors are surprisingly similar to those of humans and other animals. Their short lifespan, easily spotted mutants and ability to reproduce in large numbers have made fruit flies into a major scientific model system that has played an important role in scientific investigations from developmental biology to the testing of new drugs and identifying mutations resulting from radiation -- and of course, modern genetics would be impossible without the fruit fly. Written by Stephanie Elizabeth Mohr, a leader in the Drosophila research community, this lucid book introduces a variety of fundamental biological concepts discovered over the last century, thanks to fruit flies, and explores how Drosophila research has expanded our understanding of human health and disease, and led to effective treatments as well as a bunch of insights into important biological processes. In fact, the fruit fly has been so important to modern research that they have been the foundation for at least five Nobel Prizes. This fascinating book will especially appeal to students of the life sciences and the history of science, and to all curious people.

Lessons from the Lobster: Eve Marder’s Work in Neuroscience by Charlotte Nassim (MIT Press, 2018: Amazon US / Amazon UK)

What can thirty neurons in a lobster’s stomach teach you about the human brain? A lot, as it turns out. This engaging book by writer Charlotte Nassim tells the story of pioneering neuroscientist Eve Marder, who has devoted more than forty years of her life to studying a tiny network of neurons in the California spiny lobster, Panulirus interruptus. Compared to mammals, the simplicity of this lobster’s nervous system makes it a superb model system for generating widely applicable insights into the modulation of neural activities, equilibrium and the secrets of how neural networks function. Along the way, we learn that Marder is particularly skilled at adopting and using a wide variety of established methods in conjunction with thoughtfully-designed experiments to investigate how this neural circuit works. This brilliant book also details daily life in the lab, and reveals how Marder, “without technological fireworks or lavish funding”, is steadily working to demystify human neurobiology. It reads like a carefully-crafted detective novel, and will inspire almost everyone, especially students of neuroscience and the life sciences, and those who enjoy reading about passionate, driven people.

Buzz: The Nature and Necessity of Bees by Thor Hanson (Icon Books Ltd, 2018: Amazon US / Amazon UK)

When people talk about bees, they’re usually talking about the honeybee. However, there are tens of thousands of bee species out there, mostly overlooked, including all manner of small buzzy beasts, such as bumblebees and mason bees, leafcutter bees and solitary bees all of which are critically important to maintaining our food supply. These bees also play important roles in human history, mythology, agriculture and even economics. This fascinating book starts at the beginning -- 125 million years ago -- to share the story of the bees from that special time when a branch of ancient wasps began their transformation to veganism when they started feeding pollen to their young. This delightful and informative book is crammed with a wealth of fascinating information about bees -- including their evolution from that ancestral wasp, their different reproductive, nesting, and dietary habits, their preferred habitats as well as their agricultural value from ancient through modern times. I was especially impressed by the chapter examining the contributions of bees to all of the components of a McDonald’s Big Mac Meal because it was a creative and effective way to draw readers’ attention to the importance of bees to our everyday lives. Everyone, from bee fans and nonspecialists, to hobbyist beekeepers and professional entomologists, will learn something about the bees from this satisfying book.

Blossoms: And the Genes that make them by Maxine F. Singer (Oxford University Press, 2018: Amazon US / Amazon UK)

Besides being beautiful, flowers are remarkable structures. But how does a plant make its flowers? Only 20 years ago, no one knew the answer to this very basic question. This delightful little book explains our current understanding about flowers, starting with explaining what plants are, discussing genes and how they evolved to work in teams, and the intricate molecular biology of how plants create flowers -- their gorgeous colors, stunning varieties of petal shapes and their alluring scents -- before concluding by telling the reader about the ways that humans are the accidental beneficiaries of flowers. Along the way, we learn how plants know when to bloom, how plants construct a flower properly so its particular pollinators are attracted to it, and we learn about the sorts of genetic instructions that underpin the entire process. Despite this advance in our knowledge, there is still so much to learn. The author, Maxine Singer, is a leading molecular biologist whose writing is direct and informative and, at times, humorous. If you’ve ever been fascinated by watching flowers grow and wondered how plants make them, this fascinating book is for you. I guarantee you will never look at flowers the same way again.

Around the World in 80 Trees by Jonathan Drori (Laurence King Publishing, 2018: Amazon US / Amazon UK)

A brilliant blend of science, history, culture and folklore, this interesting and engaging book explores the relationship between people and trees as it circumnavigates the globe. Author and tree expert, Jonathan Drori, shares strange and fascinating stories about a variety of familiar or prominent trees species, from the redwoods of California, to Mexico’s avocado trees and India’s banyons, from Iran’s pomegranates, and Thailand’s rubber trees to Chile’s monkey puzzle trees, and tells about the trees that provide us with raw materials to make all sorts of wonderful things from maple syrup to aspirin. Each tree species is featured in a stand-alone vignette that is several pages long, making this book well-suited for dipping into whilst riding the subway or before dozing off to sleep. The quietly passionate writing is informative, interesting and quite delightful. The hardback version, which I’ve got, is one of the best-produced books I’ve read in years: the formatting is crisp and inviting, the paper is heavy and of high quality, and almost every page includes color drawings by artist Lucille Clerc that are simply breathtaking. Together, these features make this book a joy to touch, to hold and to read.

How to Walk on Water and Climb up Walls: Animal Movement and the Robots of the Future by David Hu (Princeton University Press, 2018: Amazon US / Amazon UK)

The innovative ways that animals move have fascinated biologists for centuries, and also have much to teach the engineers of today about how to build better robots. The author, David Hu, who studies biolocomotion at Georgia Tech, regales us with astonishing tales of animal locomotion. For example, fire ants cling together to form rafts out of their bodies that allow them to float across oceans to colonize remote islands, and cockroaches can run at the equivalent of 200mph, bounce off walls and can even be squeezed down to one-quarter of their height and still keep going. This fascinating book not only shares research into animal movement, but also discusses how this knowledge is influencing cutting-edge technology and contributing to development of avant-garde applications in physics, engineering and robotics. This highly accessible and exciting book is a quick, enjoyable adventure. If nothing else, you will certainly gain a whole new appreciation for the near-indestructibility of cockroaches.

Eye of the Shoal: A Fishwatcher’s Guide to Life, the Ocean and Everything by Helen Scales (Bloomsbury Sigma, 2018: Amazon US / Amazon UK)

As a lifelong fish-keeper, I’ve always been frustrated by people who don’t care how intelligent and truly interesting fishes are. Fortunately, marine biologist and writer, Helen Scales, has written this superb book about the fantastically diverse and rich world of the fishes, whether they live in your aquarium or in a coral reef on the opposite side of the planet. Dr. Scales starts by sharing the evolutionary history, biology, and ecology of the fishes, discusses fascinating research into their neurobiology, intelligence and memory, and details how fish glow in the dark, how they change sex, how they create colors, venoms and toxins, and explains the various methods that fish have evolved to hear and communicate -- and, this is for all us kids out here, we even learn that some fish communicate by farting. This highly readable, appealing and captivating account of the lives and behaviors of fishes will delight and inform, whether you are a professional marine biologist, a student of the sciences, an aquarist or diver, or a fascinated nonspecialist who just wants to read something different.

Eyes to See: The Astonishing Variety of Vision in Nature by Michael Land (Oxford University Press, 2018: Amazon US / Amazon UK)

Complex, image-forming eyes are amazing structures because most animals have them, and also because eyes evolved early, and independently, many times in evolutionary history. The author of this comprehensive book, Michael Land, is a British neurobiologist and a world-renowned authority on animal vision. In this captivating book, he gives a complete introduction to the eight principal types of eyes that evolved in animals, and explains some of the many elegant, ingenious experiments that have revealed how sight evolved and how it is used it to perceive the environment and to gain an advantage over other animals. Professor Land talks about the different visual systems in a variety of animals, including spiders, which have at least eight eyes, which are all adapted to different visual tasks, and the mantis shrimp, which, despite having twelve visual pigments (humans have only three), has surprisingly poor eyesight. But perhaps most interesting is that these animals’ eyes is where visual information is processed, whereas in humans, the brain is our visual processing center. The book ends by considering how constantly shifting images from our eyes are converted in the brain into the steady and integrated conscious view of the world we experience. Although this is not a textbook (Professor Land has already written one of those), the information in this book is detailed enough that its appeal may be limited to those with either some knowledge about, or a deep passion for learning about eyes and vision.

End of the Megafauna: The Fate of the World’s Hugest, Fiercest, and Strangest Animals by Ross D. E. MacPhee (W.W. Norton, 2018: Amazon US / Amazon UK)

It’s easy to forget that Africa is not the only continent that was home to giant beasts, such as elephants, giraffes, rhinoceroses and hippopotamuses. Such so-called megafauna could be found on all the world’s continents and on a great many islands as well -- crocodiles that weighed more than a ton, huge birds weighing 500 pounds, and lemurs the size of gorillas. What happened to them? In this fascinating book, paleomammalogist and writer, Ross MacPhee, asks: what caused these mass extinctions? Were we to blame? The author provides a contemporary and detailed analysis of current hypotheses for these Near Time megafaunal extinctions -- extinctions of large vertebrates and their smaller relatives that occurred around 12,000 years ago. Professor MacPhee argues that the evidence suggests that hunting, climate change, and other human activities are to blame, especially on islands. If the author’s arguments are not interesting enough for you, these now-extinct megabeasts (along with some smaller, but still living relatives) are beautifully depicted in their preferred habitats in many incredible illustrations by artist Peter Shouten that are a joy to behold, and the book also includes excellent maps and diagrams. Sadly, some paintings are double-page spreads that are split in the middle by the book’s binding, make it impossible to appreciate the complete intact artwork.

Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past by David Reich (Pantheon, 2018: Amazon US / Amazon UK)

Where did we come from and how did we get here are two of the most enduring questions that people ask, and these fundamental questions at the center of this fantastic book. Its author, biologist David Reich, who studies the population genetics of ancient humans, has been at the forefront of human genomics for his entire professional career. In this book, Professor Reich explains how the newest ancient DNA and whole genomics technologies are deepening our understanding of human origins and migration patterns as well as providing new insights into archeology, linguistics and even medical science. For example, Professor Reich discusses how the relationships between humans and Neanderthals are just one example of many where our shared genetic history resembles a complex network of intertwining lineages rather than the more traditional view of a tree whose branches separate and never rejoin. This intriguing book is probably the most up-to-date book available on this swiftly developing field, and is a great example of how technological innovations are changing our scientific and historical views of ourselves and how we came to be.

For more faboo science books, please refer to my previous annual mini-reviews of the 10 best books about biology in 2016 and 2017.

Many thanks to the publishers and their publicity agents who graciously sent review copies of their beautiful books far off the beaten track to snowy Norway.

EXECUTIVE INTERVIEW – SDP Oncology: Uncovering New Biology

In recent years, the oncology community has seen a shift in understanding how the immune system interacts with cancer cells. Researchers have learned that people’s immune systems may help fight cancer, as evidenced by the approval of multiple immune checkpoint inhibitors. While these drugs have revolutionized the treatment of cancer for some people, they don’t work for everyone. As one of its many areas of focus, Sumitomo Dainippon Pharma Oncology, Inc., a wholly-owned subsidiary of Sumitomo Dainippon Pharma Co. Ltd. based in Japan, has been committed to learning why some people benefit from immune-targeted agents and others do not. Through this research, the company has discovered that the tumor microenvironment plays a crucial role in the immune response to a tumor. David J. Bearss, PhD, Chief Scientific Officer and Global Head of Research* at SDP Oncology recently spoke with Drug Development & Delivery about the company’s unique structure that has supported its robust research in the tumor immune microenvironment as well as its investigational assets being studied in this space.

Q: What is SDP Oncology’s business model and what are the benefits of being a wholly-owned subsidiary of Sumitomo Dainippon Pharma?

A: We are a global oncology-focused company that is dedicated to developing novel cancer therapeutics that will make a meaningful difference in the lives of patients with cancer. Our efforts encompass moving programs from very early drug discovery through clinical development and commercialization. Often, big companies acquire smaller companies and then integrate them into the parent company. Recently, there’s been a movement towards keeping the smaller companies more independent, which allows the smaller company to maintain its culture, environment and nimbleness while having the infrastructure, financial support and value that comes from a large organization. You have the best of both worlds.

In addition, we have the power that comes from being in multiple geographic locations. We have research and development teams in Japan that are part of this new oncology focus. From the research side, it’s exciting for us to think that all day, every day, there’s someone working on these programs. Cancer doesn’t sleep and neither should we. SDP Oncology is always working on our programs and there is constantly somebody actively pushing forward the research behind them.

Q: SDP Oncology is a company with multiple platforms. What does this mean for your portfolio and the types of novel drugs you are discovering?

A: Because we have a multitude of drug modalities – the technologies that serve as the platform – we are not limited to the types of targets that we can pursue. I’ve always been a believer that we will follow the best biology that’s available to us. Having multiple drug modality platforms gives us access to technology that allows us to pursue any target that we think is novel and has potential. We have access to a number of drug delivery technologies as well as several approaches for target engagement. We are not constrained to just small molecules, for example. We have nanomedicine technology that allows us to change the pharmacokinetics and distribution of a drug. We have peptide conjugation technology, aptamer technology, antibody-drug conjugate technology, biomolecule conjugates and polymer conjugates, just to name a few. The proprietary technology that exists within SDP Oncology doesn’t put any limits on us with respect to pursuing biology that we find interesting.

Q: Can you describe SDP Oncology’s focus on the tumor immune microenvironment and why it is important in creating novel oncology drugs?

A: Over the past several years, there has been a shift in understanding how the immune system interacts with cancer cells. The immune checkpoint inhibitors that have been approved are among the most successful oncology drugs that we have in our arsenal today. The oncology community has discovered that our own immune system is probably the best medicine we have in fighting cancer. These drugs have been revolutionary and provided benefit for a lot of people, but they don’t work for everybody. As we’ve tried to understand why it is that some people benefit from immune-targeted agents and others do not, we’ve discovered that the microenvironment of the tumor is important.

Most tumor cells interact with the surrounding normal cells, what is called the “tumor microenvironment,” and these interactions are critical to the survival of the tumor. The cancer cells influence the cells they interact with, and that microenvironment determines if a patient will respond to an immune-targeted agent. We’ve been trying to understand what targets exist, both on cancer cells and non-cancer cells, that create an immune microenvironment that competes for resources in the tumor. We want to target the right biology that will change that microenvironment and the behavior of both the cancer cells and the immune cells within the tumor to activate an immune response.

Q: What strides has SDP Oncology made in studying the tumor immune microenvironment?

A: We’ve identified a number of new targets that we think are crucial in modulating interactions that immune cells have with cancer cells. It’s been such a dramatic change in the way that we develop drugs. In the old days, therapeutics were focused on just killing cancer cells or putting those cells into a more sensitive state so that they can be either targeted with a single agent or in combination with different types of therapy. The new biology that we are trying to uncover might not necessarily have a direct effect on the cancer cells. In fact, they may not kill cancer cells at all, but they change that microenvironment. It is challenging as a drug discovery research group to develop the right systems, the right assays, and the right models to test these types of agents. Most of the models that we use preclinically are focused on killing cancer cells and shrinking tumors that are grown in animal models. We’ve had to change those model systems to assess mechanistically what new agents are doing.

Q: Can you describe dubermatinib and its role as an AXL kinase inhibitor and the role of TP-1454 as a PKM2 activator, within the context of the microenvironment?

A: Dubermatinib is a compound we discovered in a model system that involved the zebrafish. We used the fish as a screening tool to look for a very specific biology to target the AXL protein. AXL is a receptor expressed in many cells in our body and it is responsible for sensing cell damage and cell death. When it gets activated in tumor cells, it changes the behavior of these cells, making them less differentiated, more aggressive and resistant to therapy. We refer to this state as the “mesenchymal phenotype.” We screened thousands of compounds and found that dubermatinib was the only one – in this particular model – that can reverse this mesenchymal change. AXL kinase is a tumor immune microenvironment target because not only does the cancer cell express the protein, but so do the surrounding immune cells. When activated in immune cells, it changes their behavior and makes it harder for the body to mount an immune response against the cancer. Dubermatinib has a specific effect on the cancer cells, changing this aggressive behavior, and targets the immune cells at the same time by pushing them into a more responsive state to mount an appropriate immune response against the cancer.

TP-1454 is another compound unique in its biology. Almost every drug inhibits protein activity. In this case, our drug is an activator of the PKM2 protein. PKM2 is a metabolic enzymatic “switch” that gets turned on in cancer cells. As cancer cells become more aggressive and the tumor starts to grow, the tumor changes its metabolism and its ability to utilize different types of nutrients to adapt to the changing environment in which cancer cells find themselves. PKM2 is expressed but it’s not a very active enzyme, which is of metabolic benefit to the tumor cells. TP-1454 makes this enzyme become highly active, shifting the metabolism of the cancer and starving it of certain essential building blocks necessary for growth. For years, we thought a characteristic distinguishing cancer cells from normal cells was the metabolic requirements and changes that occur during tumor formation. If you could exploit these differences, it could serve as an Achilles heel for those cancer cells. Unfortunately, as industry tried targeting these metabolic pathways, the cancer cells were quick to adapt to the changing environment. PKM2 looked like an attractive target. As we started to think about this target in the tumor immune microenvironment, we questioned whether other cells inside the tumor express the enzyme and what happens to those cells. While we know cancer cells can adapt, normal cells are restricted in what they can do. It turns out the normal immune cells inside the tumor are competing with the cancer cells for resources. To mount a reaction against the cancer, you have to take off the ”brake,” which is the immune checkpoint. But there also needs to be fuel for immune cells to proliferate quickly, in terms of energy production. It turns out that access to fuel is suppressed in the tumor immune microenvironment, in part through PKM2.

Q: Are you saying the AXL inhibitor and the PKM2 activator work together in the tumor immune microenvironment?

A: We developed them separately to target very different pathways. It’s possible these compounds may work in combination with existing agents, which we are evaluating. It’s challenging to develop two novel drugs at the same time. If we are looking at combination activity, we will take an already approved therapeutic and combine it with the new compound. It’s easier to study that because the approved drug has been validated in terms of efficacy and safety. There may be opportunities in the future to develop two novel drugs for combination at the same time.

Q: What is the status of these assets in clinical development and what can you share about the results of preclinical studies?

A: TP-1454 has an active IND and will move forward with the first-in-human study, which is just getting started. It’s a first-in-class compound that we hypothesize will change the metabolic microenvironment of the tumor and make it more permissive to an immune response. We’ve shown in animal models that treatment with TP-1454, which activates PKM2, in combination with an immune checkpoint inhibitor, produced a dramatic response. We are excited to see what happens in the clinical studies.

Dubermatinib just completed a Phase 1 study where we treated over 150 patients. Half of the patients were part of the dose escalation evaluation where we determined the safety and the maximum tolerated dose of the drug. We did an expansion from the dose escalation study to explore specific tumor types. We examined biopsies from some of the patients in this expansion study before they received treatment with dubermatinib and then took another biopsy after. We can use these to determine changes not only in the tumor, but also in the tumor microenvironment. We have analyzed these data and they were presented at ESMO 2020 Virtual Annual Congress. This data showed that dubermatinib produced changes consistent with AXL inhibition and will help us design the next clinical study as we move this program forward.

Q: Are you targeting specific cancers?

A: Every cancer is unique from a genetic and mechanistic standpoint. We are interested in identifying the characteristics of an individual patient’s cancer that make it susceptible to a specific therapy. Most cancer types, like breast cancer, share some common characteristics, so we do a lot of drug development around specific tumor types. We are also trying to group cancer types that are similar to one another at the molecular or mechanistic level. We have some ideas on why certain kinds of cancers may be more susceptible to treatment than others and we are trying to validate those quickly in early clinical development to set a clinical development path that will be most effective. We want to deliver therapy that will be as effective as possible for the individual. We also want to develop tools to identify those patients who will respond to particular therapies.

Q: What are your feelings about licensing these drug assets or working with partners?

A: Partnerships can be opportunistic if it makes sense from a development and commercialization standpoint. Part of our strategy in the short term, as programs mature, if appropriate, may involve looking for partners to address different parts of the world where we don’t yet have a presence. Part of my goal leading the research team is to develop our programs internally and to look for partners on specific programs that may not fit our clinical development strategy.

*Note: This interview was conducted before Dr. Bearss made the decision to leave his role as Chief Scientific Officer and Global Head of Research at Sumitomo Dainippon Pharma Oncology and return to academia at the University of Utah. Dr. Bearss will remain at the company as a member of its Scientific Advisory Board.

Interleukins in Cancer Biology

Interleukins in Cancer Biology responds to the growing need for credible and up-to-date information about the impact of interleukins on occurrence, development and progression of cancer. It provides reliable information about all known interleukins (38), describes recent discoveries in the field, and moreover, suggests further directions of research on the most promising aspects of this topic. The structure and presentation of the work is very understandable and clear with attention to detail maintained throughout. There are multiple illustrations throughout to help in comprehending and remembering the most important facts. .

Interleukins in Cancer Biology responds to the growing need for credible and up-to-date information about the impact of interleukins on occurrence, development and progression of cancer. It provides reliable information about all known interleukins (38), describes recent discoveries in the field, and moreover, suggests further directions of research on the most promising aspects of this topic. The structure and presentation of the work is very understandable and clear with attention to detail maintained throughout. There are multiple illustrations throughout to help in comprehending and remembering the most important facts. .


New from 2021: Tumor Biology is published by IOS Press as of January 1, 2021. The first articles were published in Volume 43 in April 2021. Content will be published on a rolling basis, with one volume and issue per year.

Recent back issues: All content in Volumes 39 to 42 can be accessed via the Sage journal platform here.

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Official journal of ISOBM: The journal is published in association with the International Society of Oncology and BioMarkers.

Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. It covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression.

Specific topics of interest include, but are not limited to:

• Pathway analyses
• Non-coding RNAs
• Circulating tumor cells
• Liquid biopsies
• Exosomes
• Epigenetics
• Cancer stem cells
• Tumor immunology and immunotherapy
• Tumor microenvironment
• Targeted therapies
• Therapy resistance
• Cancer genetics
• Cancer risk screening.

Studies in other areas of basic, clinical, and translational cancer research are also considered in order to promote connections and discoveries across different disciplines.

The journal publishes original articles, reviews, commentaries, and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication.

Magdalena Chechlinska, PhD, Dr Habil
Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw, Poland
E-mail: [email protected]

Associate Editors
Changyan Chen
Northeastern University
Boston, USA

Stefan Holdenrieder
University of Bonn
Bonn, Germany

Magdalena Kowalewska
Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw, Poland

Salvatore Piscuoglio
University Hospital Basel
Basel, Switzerland

Marta Sanchez-Carbayo
University of the Basque Country
Leioa, Spain

Editorial Board
Vivian Barak
Hadassah Medical Center
Jerusalem, Israel

Javier Castresana
University of Navarra
Pamplona, Spain

Caroline Chapman
University of Nottingham
Nottingham, United Kingdom

Chi Hin Cho
The Chinese University of Hong Kong
Hong Kong, China

Jose Luis Costa
University of Porto
Porto, Portugal

Elefterious Diamandis
Mount Sinai Hospital
Toronto, Canada

Joe Duffy
University College Dublin
Dublin, Ireland

Sten Hammarström
Umeå Universitet
Umeå, Sweden

Kohzoh Imai
The University of Tokyo
Tokyo, Japan

Chien-Feng (Angelo) Li
Chi Mei Medical Center

Leendert H. J. Looijenga
Erasmus MC Cancer Institute
Rotterdam, The Netherlands

Andrea Nicolini
University of Pisa
Pisa, Italy

Barbara Pedley
University College London
London, United Kingdom

Johanna (Hanny) M.A. Pijnenborg
Radboud University Medical Center
Nijmegen, The Netherlands

Ulf Hakan Stenman
University of Helsinki
Helsinki, Finland

Iwona Wlodarska
Katholieke Universiteit Leuven
Leuven, Belgium

Tumor Biology, launched in 1980 (formerly published as Oncodevelopmental Biology and Medicine), is a peer reviewed, open access journal publishing experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines.

The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous single-blind peer review and are selected on the basis of whether the research is sound and deserves publication.


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When experimental animals are used, the Materials and methods section must briefly but explicitly state measures which were taken to minimize pain or discomfort, e.g. type and dose of anaesthetic used. Experiments should be carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC) or with the Guidelines laid down by the NIH in the US, available from the Office of Laboratory Animal Welfare, National Institutes of Health, Department of Health and Human Services, RKLI, Suite 360, MSC 7982, 6705 Rockledge Drive, Bethesda, MD 20892-7982, or online ( .htm#pol) regarding the care and use of animals for experimental procedures.

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[1] Rose ME, Huerbin MB, Melick J, Marion DW, Palmer AM, Schiding JK, et al. Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury. Brain Res. 2002 935(1-2): 40-6. doi: 10.1016/s0006-8993(02)02445-9
[2] Murray PR, Rosenthal KS, Kobayashi GS, Pfaller MA. Medical microbiology. 4th ed. St. Louis: Mosby 2002.
[3] Berkow R, Fletcher AJ, editors. The Merck manual of diagnosis and therapy. 16th ed. Rahway (NJ): Merck Research Laboratories 1992.
[4] Meltzer PS, Kallioniemi A, Trent JM. Chromosome alterations in human solid tumors. In: Vogelstein B, Kinzler KW, editors. The genetic basis of human cancer. New York: McGrawHill 2002. p. 93113.
[5] Canadian Cancer Society [homepage on the Internet]. Toronto: The Society 2006 [updated 2006 May 12 cited 2006 Oct 17]. Available from:

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Tumor Biology is a peer-reviewed journal. Articles submitted to the journal undergo a single blind peer review process. This means that the identity of the authors is known to the reviewers but the identity of the reviewers is not communicated to the authors.

After automatic plagiarism screening through iThenticate, all submitted manuscripts are subjected to initial appraisal by the Editor-in-Chief and, if found suitable for further consideration, to rigorous peer review by independent, anonymous expert referees. Reasons to reject a paper in the pre-screening process could, for example, be that the work does not fall within the aims and scope, the writing is of poor quality, the instructions to authors were not followed, or the presented work is not novel.

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As a standard policy, decisions are based on 2 reviews. The Editor in Chief strives to ensure a typical turnaround time of 3 months.

Reviewers are asked to judge a paper on at least:

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Based on the received reviews the handling editor will propose to the Editor in Chief a recommendation:

Community Reviews

Cowan starts with a pretty interesting take on the history of cancer treatment. He poses some great questions as well! It set up would could have been a very engaging read on shortcomings in the field, and highlighted promising research and new avenues of thinking.

He then decides to hault everything and spends 1/4th of the book giving you a high school biology lesson. This was an absolute slog, and I don&apost think it added much other than to show us that Cowan is capable of paraphrasing a textbo Cowan starts with a pretty interesting take on the history of cancer treatment. He poses some great questions as well! It set up would could have been a very engaging read on shortcomings in the field, and highlighted promising research and new avenues of thinking.

He then decides to hault everything and spends 1/4th of the book giving you a high school biology lesson. This was an absolute slog, and I don't think it added much other than to show us that Cowan is capable of paraphrasing a textbook. I would understand if this acted as the basis for later points. But he simply explains a few fundamentals, lightly touches on their importance, and that extrapolates like crazy.

The last half of the book is one anecdote after another about how someone cured their cancer by eating turmeric. I honestly think Cowan flexed his "science muscles" earlier to fool people into thinking his points are based in science. He provides terrible comparisons along the lines of "chaga mushrooms look like cancer, and grow on birch trees. Guess which kinds of trees don't get cancer!?"
I'm oversimplifying - but so is he. For someone who is so critical of research and modern sciences, he felt overly willing to throw away sound scientific basis and quality research for his BS.

The worst thing is that he has the odd good idea, or semi salient point. But please don't go to this man for answers! Maybe he'll get you thinking about a few aspects of modern medicine? But don't expect to actually learn anything real or significant.

I hate to use the word quack. But in the later half of the book, he reeeally pushed into quack territory. . more

Science, physics and chemistry: Art, robeen evaded by?) mainstream caregivers. After nearly 40 years of the "War on Cancer" spending billions of dollars, Cowan posits that "the current path represents a fundamental misunderstanding of the nature of life, and therefore the nature of cancer."

The most empowering aspect of this book is Cowan&aposs calm delivery of doable options that for the most part, can be undertaken independently from mainstream caregivers.

Science, physics and chemistry: Art, robeen evaded by?) mainstream caregivers. After nearly 40 years of the "War on Cancer" spending billions of dollars, Cowan posits that "the current path represents a fundamental misunderstanding of the nature of life, and therefore the nature of cancer."

The most empowering aspect of this book is Cowan's calm delivery of doable options that for the most part, can be undertaken independently from mainstream caregivers.

Noticing I skipped writing a review of this book. I have some ambivalence about it. It’s a bit of a somewhat superficial mish mash — and something about it made it hard to read and absorb. As an alternatively minded stage 4 cancer patient I’d think I’d gobble this book, but I felt strangely separated from it. My own resistance? Feeling like I should do everything I can, but all the ideas are just kind of exhausting.

Fundamentally I’m thrilled with his idea of the 4th phase of water and that we a Noticing I skipped writing a review of this book. I have some ambivalence about it. It’s a bit of a somewhat superficial mish mash — and something about it made it hard to read and absorb. As an alternatively minded stage 4 cancer patient I’d think I’d gobble this book, but I felt strangely separated from it. My own resistance? Feeling like I should do everything I can, but all the ideas are just kind of exhausting.

Fundamentally I’m thrilled with his idea of the 4th phase of water and that we are all batteries generating energy for our biological processes in a way that hasn’t been appreciated in the mainstream. This concept is also explores in Sayer Ji’s book, Regenerate if anyone is interested. Cowan is a creative cutting edge free thinker, and I wish sometimes that I could read a companion voice that would double check and pressure test his ideas. He tosses out a lot of stuff that then often leaves the reader without practical or affordable ways to work with or implement the ideas. It doesn’t negate the information, but leaves me a little bit cool about it all. . more

There&aposs a theme in tales of the Old West about a lone gunslinger who rides into town to fight evil and injustice, ultimately triumphing despite the powerful forces arrayed against him. It&aposs also a popular theme among supporters of alternative medicine.

Thomas Cowan is one of the latest Brave Mavericks to arrive on the scene, defying conventional medical wisdom. In previous books he assured us that vaccines cause autoimmune diseases (they don&apost) and that the heart is not a pump (huh?). In "Cancer There's a theme in tales of the Old West about a lone gunslinger who rides into town to fight evil and injustice, ultimately triumphing despite the powerful forces arrayed against him. It's also a popular theme among supporters of alternative medicine.

Thomas Cowan is one of the latest Brave Mavericks to arrive on the scene, defying conventional medical wisdom. In previous books he assured us that vaccines cause autoimmune diseases (they don't) and that the heart is not a pump (huh?). In "Cancer and the New Biology of Water" Cowan explores his belief that cancer is caused by derangements in the intracellular structure of water.

You see, oncologists and cancer researchers are all wrong by focusing on genetic mutations and known toxic exposures (i.e. smoking and excessive alcohol consumption) as causes of cancer. Cowan has decided that a host of other things, including glyphosate and EMFs from cellphones and computers are to blame, and this somehow ties in to our precious intracellular bodily fluids. Since there is virtually no good science in support of this theory, Cowan seems to have arrived at it through intuition and occasionally observation. One of his early revelations came when he worked at an ER and discovered that his instructors were wrong about the human body being mostly composed of water, since he observed lots of trauma patients and they were never gushing out water, just blood.

The rest of the book's haranagues about water range from the comical to the bizarre, as when Cowan eloquently describes the moment of conception as a "merger of the dense, nuclear male side and the watery, maternal feminine side."

Cowan attacks the mainstream medical community for not plowing major resources into investigating alternative cancer therapies long ago discarded as useless or outright quackery. He praises such figures as Royal Rife and Max Gerson and provides a list of interventions and supplements that are supposed to help cancer patients. These include consumption of bone broth, mistletoe, "Quinton Isotonic Seawater", deuterium-depleted water, special diets (including eating only at certain times of the day), NADH, EMF bracelets and coffee enemas. Numerous supplements that he recommends are ones Cowan sells or distributes through his website.

It's sad to think of cancer patients wasting money and time cramming down handfuls of supplement pills, drinking enormous quantities of fruit and vegetable juices, eliminating favorite foods and undergoing coffee enemas. An illustration of the futility of such practices was provided recently in a formal study comparing use of a Gerson-style protocol vs. conventional chemotherapy in treating pancreatic cancer patients. The outcome showed that the juice/supplement/coffee enema group had significantly shorter survival and poorer quality of life than the conventionally-treated group.

It should be noted that false claims about water structure and the promotion/selling of "special" water to improve health is old hat in the world of woo. The website is a good source of information.

Be advised though that if you don't take Doc Cowan's advice there are apocalyptic consequences. As he warns, "Either we can wake up to our true nature, and soon, or we are destined to destroy everything.
Which will you choose?"

Cancer Biology: Getting Down to Basics with Bob Weinberg

Who would have thought that cancer research pioneer Robert A. Weinberg, PhD, had another, more rustic, pioneering side to him?

During an exclusive interview with MedPage Today, the much-decorated molecular biologist expressed great pride in the 1,200 square-foot stick-frame cabin he'd built by hand over the years in the woods of New Hampshire, as well as an accompanying gazebo and other wooden structures.

In fact, the man widely known for his discoveries of the first human oncogene and the first tumor suppressor gene confessed that if he hadn't become a scientist, he might have considered a career in carpentry. He said he was also very much committed to gardening and compiling his family's genealogy, which he has traced back to 1675 in Westphalia, Germany.

As a young boy whose original language was German (his parents fled Nazi Germany) and who had to lose an accent, Weinberg was intrigued by all things mechanical, and spent time with his maternal grandfather who repaired sewing machines in the family's basement.

Two of his most useful courses in grade school were woodshop and mechanical drawing, he said, noting how they later helped in developing skills for his avocation and vocation.

In 1976, before he'd even received tenure at MIT, where he has spent nearly all his professional career, he bought a plot of land "as an act of faith" in New Hampshire and started building the first section of his cabin over the next two years, before adding two more wings and a porch during the next decade or so.

Weinberg said that he was hard-pressed to prove it, but he wondered whether some of the same neural circuitry that explained his interest in carpentry and physical structures somehow helped him think through biological problems.

Now 74, Weinberg said he has no plans to slow down and that he fears the loneliness and isolation of retirement.

Earned and Unearned Runs

Weinberg began studying viral oncogenes in 1977 leading to his seminal discovery of the first cellular oncogene Ras in mammalian cells in 1979, which he said was "an earned run" because of the hard, feverish work involved in identifying, isolating, and cloning it over the years.

However, he termed his subsequent discovery of the first tumor suppressor gene Rb in 1986 as "an unearned run," since he credited that find as having fallen into his lap thanks to the enthusiasm of Stephen Friend, MD, PhD.

"Steve wanted to clone the retinoblastoma gene and didn't know much about molecular biology. I was amused by it but didn't know if it could be done," he said, adding that Friend was undeterred and began working with a colleague across the river at Massachusetts Eye and Ear Infirmary who had already done some rough chromosomal mapping of the Rb gene.

According to Weinberg, the gene was isolated within six months through "some strokes of luck, which in this case, favored the prepared mind."

"I encouraged Steve and gave him advice, but he is the architect of isolating the retinoblastoma gene and should get the credit even though it happened on my watch in my lab," he explained.

Weinberg has spent much of his life at MIT, where he is a founding member of the Whitehead Institute for Biomedical Research, professor of biology, and director of the Ludwig/MIT Center for Molecular Oncology.

A Pittsburgh native, he applied to MIT for his undergraduate work because a family friend had gone there. At first Weinberg intended to study medicine until he learned that "doctors have to stay up all night seeing patients." Since he preferred sleeping he switched majors his sophomore year to biology, a subject he had omitted in high school.

For the past two decades he and Eric Lander, PhD, have been co-teaching introductory biology at MIT. Teaching is part of the ethic at MIT and it is not considered honorable or acceptable not to teach, Weinberg said, noting that teaching is the "best way to sharpen one's mind and mouth especially when explaining complex concepts of science."

Ironically, when he took that same course in 1961 he received a "D," the disclosure of which always draws applause from his current students, according to Weinberg.

Following graduation he continued his studies at MIT, noting that his grades probably weren't good enough for other PhD programs, but at least the faculty at MIT knew him, he said.

Stint in Alabama

But after one year in the graduate program he took a year off to head south to teach at Stillman College, the historically black liberal arts college in Tuscaloosa, Ala. It was 1965, in the midst of the Civil Rights movement, and Weinberg spent his weekends carrying rice and flour to tent cities housing sharecroppers who had been evicted from their land for registering to vote.

He said that he was not a willful activist but was rather living his convictions and saw himself as "providing useful logistical support."

However, Weinberg's stay in Alabama came to an end when Stokeley Carmichael, who would become chairman of the Student Nonviolent Coordinating Committee, "put his hand on my shoulder, and said, 'Bob, I think what you are doing now is getting a little too political,' Weinberg recalled.

He returned to MIT and received his doctorate three years later, followed by two 18-month post-docs at the Weizmann Institute of Science in Israel and the Salk Institute for Biological Studies in La Jolla, Calif. He said he was very fortunate that he was exposed to the nascent field of molecular biology while in Cambridge.

While at Salk, future Nobel laureate Salvador Luria, MD, paid Weinberg a visit and didn't ask him but told him that he was going to be part of the MIT cancer center Luria was founding.

At MIT, Weinberg was a research associate to David Baltimore, PhD, who would receive the Nobel Prize a few years later for discovering reverse transcriptase. One of the two other recipients that year in 1975 was one of Weinberg's mentors at Salk, Renato Dulbecco, MD.

Working with Baltimore, Weinberg began to explore retroviruses in his own lab, which eventually led to Weinberg's discovery that normal cells can become cancerous through exposure to chemical carcinogens through gene transfer, proving that cancer is a genetic disease and marking the scientific highlight of his career in 1979.

Over the years, Weinberg has continued his lab work, received numerous awards (including the National Medal of Science, Keio Medical Science Prize, and Breakthrough Prize in Life Sciences), and published, among many papers and books, the seminal paper (with Douglas Hanahan, PhD, in 2000), "The Hallmarks of Cancer," as well as the textbook, The Biology of Cancer, and two more general-interest works, One Renegade Cell: How Cancer Begins, and Racing to the Beginning of the Road: The Search for the Origin of Cancer.

Recently, Weinberg had a setback when several of his papers were retracted. He blamed a junior member of his lab for using "inappropriate methods for summarizing and presenting data" that Weinberg did not question at the time.

He told MedPage Today that within a day of realizing there was an issue, he told the director of the Whitehead Institute that he had grave doubts about the papers, but that it took months before the "machinery of retraction was finally manifested in the journals in which his papers were published."

Weinberg added that he has often mentioned and discussed with colleagues the strong dependence researchers have on those they work with.

"It was a painful and unpleasant interlude in my career -- the only time in 40 years that I have been duped -- and it certainly did not lend credibility to the work of my lab," he said. Still, he noted, his lab has continued to publish in topflight journals, and the experience "did not shake even a little my trust in those who work with me and their integrity."

Basic Science's Primacy

Weinberg has long been outspoken about the vital importance of basic science, noting that most innovative science and creative ideas have occurred in small groups that collaborate with others when it's advantageous and don't collaborate when it isn't.

He is not a fan of the current trend of funding large consortia research efforts that are often micromanaged by granting agencies or supervisors, and often don't encourage innovation and creativity.

He said that he would probably have joined the recent March for Science had he not been abroad at the time, but added that he thought the overall effort might have been diminished by certain scientific subgroups pushing specific agendas.

More than a decade ago he railed against cutbacks in the basic sciences that could lead to a lost generation of researchers and that has subsequently resulted in a "palpable decrease in the quality of students going into biomedical basic research."

He had few words of encouragement regarding the current administration's attitude toward science, and expressed concern over similarities he sees between today's political environment and the one that forced his family to escape from Germany in 1938.

He is also deeply worried about the future of biomedical research in this country due to, among other things, a shortfall of native-born talent as well as the less-than-welcoming environment for foreign-born researchers.

During last month's American Association for Cancer Research annual meeting in Washington, D.C., Weinberg asked how many of those attending his lecture were from abroad, and told them that American science would only be a "faint shadow of what it would have been" if they had not come here.

He said that they were critically needed and should continue attending scientific meetings and working in laboratories in the U.S.

"Without you our science would be nothing. You are welcome here with open arms," he said, eliciting a round of applause perhaps reminiscent of those heard in the MIT auditorium housing his introductory biology class.

Oral Mucositis in Head and Neck Cancer: Risk, Biology, and Management

Of the toxicities associated with conventional forms of treatment for head and neck cancers, probably none has such a consistent legacy as oral mucositis. 1 Despite the fact that mucosal injury was noted as far back as Marie Curie's first forays into therapeutic radiation, an effective intervention has yet to be developed. In addition to its historic link to radiation, new therapeutic strategies including induction chemotherapy often produce mucositis, and targeted therapies appear to alter mucositis risk and its severity and course. 2 The symptomatic effect of oral mucositis is profound. Disabling oral and oropharyngeal pain prevents patients from eating normally, requires opiate analgesics, and in some cases results in alteration or discontinuation of anticancer therapy. 3 Furthermore, the health and economic consequences of oral mucositis are far from trivial. The incremental cost of oral mucositis in patients with head and neck cancer exceeds $17,000 (USD). 4

Oral mucositis is among the most common toxicities of standard chemoradiation regimens used to treat head and neck cancers.

Risk of mucositis is largely determined by genetic factors.

The pathobiology of mucositis is complex. The mechanistic complexity of mucositis provides targets for intervention.

Mucositis in patients being treated for head and neck cancer remains a substantive, unmet clinical need.

Although the incidence of mucositis has been described as almost ubiquitous among patients with head and neck cancer treated with conventional chemoradiation regimens, there are clearly differences in the frequency and severity of its manifestations. The lack of uniform scoring criteria, variability of reporting thresholds (some studies only report grades 3 or 4), differences in the biologic challenge as a consequence of variations in chemoradiation treatment regimens, radiation fields, and tumor location have resulted in inconsistent incidence reporting. Furthermore, there continues to be a disconnect between health care professionals and patients relative to their assessments of the presence, severity, and effect of mucositis. The rate, symptom severity, and influence of mucositis on quality of life is routinely perceived as being greater among patients than the medical literature would suggest. 3 This might reflect the common and understandable attitude among those charged with treating the cancer that a marginally tolerable level of collateral damage to normal tissue is an acceptable price for tumor eradication. It is unclear what the acceptable level is from a patient's perspective, and it probably varies from patient to patient. Couple all of this with the realization that not all patients are at equal risk for mucositis, and it becomes easier to understand the reported range of mucositis frequency from as low as 30% to 40% to almost 100% when all severities of mucositis are evaluated. 5,6

Mucositis incidence data surrounding intensity-modulated radiation therapy (IMRT) is illustrative of the lack of consistent reporting. 7 -9 Many studies report mucositis incidence in patients being treated for head and neck cancers. While some reports are limited to cancers of the mouth, others are less restrictive in their inclusion criteria and include patients with cancers of the nasopharynx, sinuses, hypopharynx, and larynx as well as the mouth and oropharynx. Interpretation of results must account for this variation because it appears that the risk of significant (this definition varies from including all ulcerative mucositis to only grades 3 and 4) mucositis is markedly influenced by tumor location, as it affects the volume of oral mucosa that is exposed to radiation. The use of concomitant chemotherapy, now the standard of care, enhances mucositis risk and apparently, so does the concomitant use of targeted agents.

Regardless of the criteria used to assess the presence of mucositis in patients with head and neck cancers, it is clear there is a cohort of patients who go through treatment relatively unscathed by the toxicity. This observation has fueled speculation and studies on the topic of mucositis risk determinants. Approximately 30% of radiation therapy-induced side effects are attributable to therapy-related or patient-specific factors. A radiation dose–response analysis recently described by Bhide et al demonstrated the effect of different dose-response schedules on the development of mucositis. 10 In general, the volume of oral mucosa that receives weekly cumulative doses of 9.5Gy to 10Gy is likely to determine overall mucositis risk among susceptible patients. But even at this dose, about one-third of patients will not develop the condition. Likewise, among patients receiving cycled induction chemotherapy, almost one-half develop ulcerative mucositis, while the other half survive three cycles of treatment with no appreciable mucosal injury. Consequently, one must conclude that risk is largely a function of patient-related, not treatment-related, factors. 11

The pursuit of understanding patient-related mucositis risk factors is not new. Historically, it has centered on gender, body mass, age, comorbidities, and lifestyle. 12 Although there is some data to support each of these, it is sparse and far less convincing than one might expect given the discrepancies in mucositis frequency. More recently, the potential role of genetics has surfaced as a more likely explanation. 11

Genetic risk factors for regimen-related mucositis have been primarily studied in patients with non-head and neck cancer. Both individual and clusters of pathway-related single nucleotide polymorphisms (SNPs) have been reported to increase mucositis risk. In contrast, to date, studies of genetic risk of mucositis in head and neck cancer have been limited to evaluating radiosensitivity and its relationship to DNA repair. The genome-wide association study methodology or more sophisticated forms of analysis have not yet been applied. Rather, candidate gene/SNP studies have been the norm and have identified polymorphism associated with the XRCC1 as being predictive of mucosal injury. 13,14 Given the successes of SNP-based toxicity risk prediction studies in patients undergoing stem cell transplant or cycled chemotherapy, it seems likely that a broader look at both genes and SNPs that takes into account gene/SNP interacting networks should be fruitful in identifying actionable elements of mucositis risk prediction.

The pathogenesis of mucositis is a study of multiple sequential biologic events coupled with the influence of the oral environment and microbiome. 1 The majority of pathways that lead to mucositis are the same whether the initiating event is chemotherapy (as in induction), radiation, or concomitant chemoradiation. However, the schedule of biologic challenges is clearly different. Whereas patients being treated with cycled chemotherapy receive an acute challenge that is administered systemically, patients undergoing radiation receive a succession of fragmented (fractionated) radiation doses, which, even in small increments, trigger a cascade of biologic events. Although radiation is considered to be focally administered (vs. systemic), the biologic events it triggers are detectable systemically with resulting constitutional effects. In both cases, what has been described as ‘bystander” events result in collateral injury when products or signals from one cell (potentially the targeted tumor) negatively affect normal adjacent cells. 15

The oral mucosa shares its neighborhood with a multitude of microorganisms: bacteria, viruses, and fungi. Although the modulating influence of microbes has been studied relative to cancer regimen–related toxicities in other areas of the gastrointestinal tract, studies of their effect on oral mucositis have been largely limited to descriptions of quantitative or qualitative changes. 1,16 Mucositis is not an infectious disease. Its frequency is not affected by decolonization or antimicrobial strategies. The kinetics of bacterial colonization follows, rather than precedes, mucositis development. 1 Although there are changes in the composition of the bacterial flora in patients who are myelosuppressed and were first described almost 40 years ago, modifying the oral bacterial composition has not proven to be an effective mucositis deterrent. Furthermore, antibacterial strategies for mucositis interventions have been ineffective. 17

The role of viruses, particularly herpes simplex (HSV), in the etiology of radiation-induced mucositis remains questionable. Advocates for such a relationship cite observations of culturable HSV in a limited proportion of patients who have clinically significant oral mucositis. 18 They also suggest that treatment with standard antiviral therapy favorably affects the subsequent course of mucositis. Since over one-half of patients have latent HSV-1 infection, it is not unexpected that virus, activated by radiation or local tissue injury, would be detectable in some patients with mucositis. Consequently, although not a primary driver of mucositis, HSV-1 presence in a secondary infection could affect the course of the condition. The effectiveness of prophylactic administration of antiviral medication to patients who are seropositive and on radiation-induced mucositis has not been adequately investigated.

The oral environment is also unique relative to the presence of saliva. The fluid is a rich mix of enzymes, antibodies, and proteins that play an important role in maintaining the homeostasis of the oral mucosa and limiting microbial colonization. Because patients being treated with head and neck radiation routinely demonstrate signs of xerostomia, it was not unreasonable to suspect that a change in either the quantity or quality of saliva might affect the course of mucositis. However, this does not appear to be the case to any significant extent and certainly not in the context of a potential interventional strategy. In fact, the course of mucositis has been unaffected when saliva production–stimulating agents have been tested. 19,20

Nonetheless, additional studies are probably justified to determine the true effect of saliva on tissue. For example, are patients with preexisting conditions that lead to xerostomia more likely to develop mucositis?

The conclusion that mucosal injury is the consequence of a multifactorial cascade of biologic events is relatively new. 21 In the realm of radiation injury, direct cell damage culminating in DNA strand breaks is still relevant, but it's not the only show in town. Although the basal cells of the epithelium are the consummate “end organ” leading to tissue destruction, the pathways that lead to their demise are multiple. Although the biologic stages originally noted to describe the sequence of mucositis remain fundamentally correct, accumulating data demonstrate that their complexity is more involved than was originally described. Also, although compartmentalization of the events associated with mucositis is undoubtedly a fantasy created for the convenience of explanation, the sequence can be divided into five stages: initiation, upregulation/activation, signal amplification, ulceration, and healing. The initiating biologic events that start the process were first attributed to oxidative stress and the generation of free radicals. Although still a critical event, we now know that activation of the innate immune response and Nrf2 provides alternative initiating pathways. Studies in which these pathways have been effectively interrupted demonstrate mitigation of downstream injury. From an interventional standpoint, the initiation phase is a ripe target as its attenuation affects the course of direct and indirect pathways of tissue damage.

The free-radical scavenger, amifostine, was among the first drugs used for mucositis intervention. 22 Originally developed for the military, the clinical utility of its radioprotective effects were applied to mollify salivary gland damage and consequent xerostomia. Its application as a mucoprotective has generated interesting but inconsistent results. Especially interesting is the observation that amifostine is capable of activating genes associated with superoxide dismutase, itself capable of attenuating oxidative stress. Supporting a potential therapeutic opportunity have been results of preclinical studies in which superoxide dismutase mimetics have been effective in diminishing the intensity and course of radiation-induced mucositis and novel gene transfer studies that have reached the same conclusion. 23 In a similar way, studies with n-acetyl cysteine—an established antioxidant with the ability to affect nuclear factor-kappa beta (NF-κB) activity—have demonstrated efficacy in both animal and human studies. Finally, as noted below, palifermin's (keratinocyte growth factor 1) ability to reduce radiation-induced mucosal damage is likely due, in part, to the molecule's effect on glutathione activity. 24 Additional support for this hypothesis is the finding of increased risk of mucositis among patients who express SNPs associated with gene mutations associated with glutathione synthesis.

Following initiation, another series of cell-based events is triggered. At least 14 canonical pathways have already been associated with the development of mucositis in patients being treated with concomitant chemoradiation for head and neck cancers. 25 Among the best studied is activation of the NF-κB pathway and consequent generation of proinflammatory cytokines. 26 Although tissue and peripheral blood levels of proinflammatory cytokines—such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)—track well with the development of mucositis, it is unclear whether their role is one of mediating or messaging for injury or whether they are themselves true drivers of damage. This is especially true in the case of radiation-induced mucositis where repeated fractional challenges cause a challenge dynamic different from that associated with the acuity of chemotherapy. This is an area that requires more investigation, particularly in determining prevention and treatment strategies. Studies with agents known to mediate TNF production have been clinically tested with mixed results. Of potential importance is the finding that polymorphisms associated with TNF production are associated with chemotherapy toxicity risk prediction. It is well known that, in a variety of inflammatory diseases that result in mucosal injury (i.e., inflammatory bowel disease), an antagonistic group of cytokines—the anti-inflammatory cytokines such as IL-4, IL-10 and IL-11—likely have functional significance. 27 Given the complexities of mucositis, it would be naïve to not consider the potential role of these molecules in the overall pathogenesis of the condition. However, there current data is limited.

In theory, pharmacologics or biologics that alter cytokine expression or levels represent a potential therapeutic approach, and a number have been evaluated. Benzydamine HCl (BZD) is an anti-inflammatory rinse that has been approved outside the United States for use in patients receiving radiation therapy. Its efficacy is modest and limited to patients receiving standard radiation regimens in the absence of concomitant chemotherapy. 6 BZD has been reported to have a range of biologic activities that interfere with mechanisms thought to be of importance in the pathogenesis of radiation-induced oral mucositis. A study in a hamster model of mucositis—in which the effect of topically applied BZD on selected morphologic and biologic parameters was studied in temporal fashion—demonstrated that BZD modified epithelial proliferation, but not differentiation, and that the observed changes correlated with a reduction in tissue levels of IL-1β and TNF-α, but not IL-6. Preferential antiapoptotic activity was seen in epithelium and connective tissue of BZD-treated animals. 28

Another cytokine-based approach capitalized on the anti-inflammatory activities of IL-11. Subcutaneous injection of the cytokine favorably altered the course of mucositis induced by either chemotherapy (5-FU) or radiation in animal models. When studied in association with radiation-induced mucositis, it appeared that IL-11 suppressed the expression of genes associated with IL-1β, TNF-α, IL-2, and transforming growth factor-beta. Furthermore, the timing of modified gene expression corresponded with observed mucosal injury. Tissue levels of IL-1β and TNF-α were also suppressed in association with better clinical outcomes. 29 A clinical trial in patients receiving autologous stem cell transplantation for breast cancer was stopped before accrual could be completed.

Two agents known to inhibit TNF-α production have been evaluated in preclinical and clinical studies of mucositis associated with chemotherapy. Pentoxifylline was effective in delaying clinical manifestations of chemotherapy-induced oral and intestinal toxicity in animal models and also ameliorated oral mucositis associated with conditioning regimens for stem cell transplant. 30 -32 However, it was also associated with a higher rate of infection, suggesting that the physiologic cost of such an approach in patients who are myelosuppressed may exceed its antimucositis benefit. Nonetheless, the observation does provide a glimpse of a potential intervention strategy.

Given the finding that multiple pathways simultaneously contribute to mucositis, it seems very likely that a truly effective agent will be characterized by mechanistic pleotropism. 24 Palifermin, keratinocyte growth factor-1, was approved for the prevention and treatment of oral mucositis in patients with hematologic malignancies who received stomatotoxic conditioning regimens for hematopoietic stem cell transplants and serves as a prototype for a pleotropic antimucostitis agent. The phase III trial on which palifermin's approval was based on the mandated use of total-body irradiation as a conditioning regimen component. Subsequent trials of palifermin's efficacy have not been as consistent, but in general, the overall trend speaks to its utility for a mucositis indication. For the purposes of this discussion, the collective biologic effects of the molecule are illustrative of a multitargeted biologic shotgun. As related to initiation, palifermin has the ability to upregulate enzymes associated with the disruption of reactive oxygen species. In particular, glutathione-S-transferase and glutathione peroxidase are favorably impacted. And indirectly, palifermin's ability to upregulate Nrf2—which itself has been shown to reduce oxygen free radical damage—has been observed. Palifermin likely affects clonogenic cell death by preventing DNA strand breaks through its activation of DNA polymerases and its antiapoptotic effects implemented during the upregulation phase (probably through NF-κB) through Bcl-2, Bax, and p53 enhanced cell survival. Although palifermin resonates as a growth factor, its ability to modulate both pro- and anti-inflammatory cytokines provides a means for it to actively attenuate the cytokine-mediated tissue-damaging and amplifying effects. There is also evidence to suggest that palifermin has the potential to mitigate the effect of reduced epithelial turnover, and this is manifested in reductions in the atrophic and ulcerative changes that characterize mucositis. As one would predict based on its fundamental growth factor activity, it appears likely that palifermin favorably affects events associated with epithelial injury. However, the inconsistencies reported in palifermin's clinical efficacy seem puzzling given its biologic robustness and point to some of the challenges in developing an effective mucositis intervention.

Clinical data for palifermin as a mucositis intervention now exist for conditioning regimens for both autologous and allogeneic hematopoietic stem cell transplantation chemotherapy used for the treatment of colorectal cancer, head and neck cancer, and sarcoma and a smattering of regimens for hematologic malignancies. Positive efficacy signals have been reported for most but not all. The variability of responsiveness is confusing and might reflect individual dose response, responsiveness to keratinocyte growth factor or a range of other possibilities. What seems clear is that, as shown with other mechanistically based approaches to mucositis treatment, not all patients respond in the same way, and to optimize efficacy, a personalized approach to intervention—understanding risk and response/nonresponse—is highly desirable.

Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate family member those marked “B” are held by the author and an immediate family member. Relationships marked “U” are uncompensated.

Employment or Leadership Position: Stephen T. Sonis, Biomodels (L). Consultant or Advisory Role: Stephen T. Sonis, ActoGeniX Axaxia Biologicals Galera Therapeutics (U) Inform Genomics Izun Pharmaceuticals Merck Novartis Pfizer Polymedix (U) ProCertus SciClone. Stock Ownership: None. Honoraria: None. Research Funding: None. Expert Testimony: None. Other Remuneration: None.