On Cancer: Bowie, Bullets, and Bathtubs
Cancer touches us all, either directly or indirectly. This piece speaks to a variety of aspects including treatments and resources for general information.
Heather I. Thompson CQA, CMQ/OE, is new to the blog. She has a B.S. in Biochemistry and Molecular Biology, and is completing a Pharmaceutical and Medical Device Regulatory M.S. (May 2016) from the University of Maryland School of Pharmacy, following over 15 years working in biopharma and Quality Management. She is a professional beginner knitter, cowgirl boot aficionado, and is interested in the intersect between rapid diagnostics, antibiotic resistance, and stewardship programs, particularly in pediatrics. Heather is also a frequent contributor at the Pharma Skepti-Forum.
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I’ve been thinking about cancer…
Cancer has been taking up a lot of my thoughts lately, as it has many others’, given the recent cancer-related deaths of some of our biggest icons, e.g., David Bowie. Even President Obama laid out a plan a few weeks ago in his final State of the Union address. With so many of us directly or indirectly touched by this collection of diseases we call “cancer”, it’s in the public consciousness. This leaves many angrily asking, “Why do so many people get cancer?” Oncology therapeutics are the largest pharmaceutical market, and one of the latest presentations by an FDA employee that I attended reiterated that ~48% of men and ~38% of women will be affected. I’ve had two colleagues and one friend who had breast cancer; I have an immediate family member who has lymphoma, among others I know and love. If we use the term “affected” to mean those with a family member or friend with cancer, in addition to the actual patients, the number is closer to 100%. No wonder it’s a large market. And the numbers are expected to grow.
In addition to this emotional impact, I’ve also written on drug-induced hepatotoxicity (sorry folks, not published online) with chemotherapeutic mercaptopurine, a pharmaceutical sledgehammer akin to nitrogen mustard; therapeutic misconception, i.e., the misconception that participation in clinical research is the same as medical care and treatment, which strongly figures into informed consent for trial participation as a subject particularly for the very ill; and the targeted antibody-drug conjugate ado-trastuzumab emtansine for HER2+ breast cancer. Brand named “Kadcyla” by Genentech, you may recognize the monoclonal antibody component trastuzumab by its brand name “Herceptin”. The Hodgkin Lymphoma MOPP regimen (nitrogen mustard or “mustargen”, vincristine or “oncovin”, procarbazine, and prednisone) developed at the NCI in the 1960s was the first combination chemotherapy and remains in use today, along with the similar CHOP (cyclophosphamide, “hydroxy” doxorubicin, vincristine, and prednisone) that may also include rituximab (R-CHOP) used currently to treat Non-Hodgkin Lymphoma.
Meanwhile, researchers are working on lowering the amount of chemotherapy needed and focused diagnostics, like the HER2+ diagnostic used in focusing breast (and other) cancer treatment. In January, research showed how developing cells switch from a primitive stem-like state to a specialized state and how an EGFR receptor HER-2 protein signaling process mediated by Tel-1 protein transcription factor might go wrong in cancer, and on the diagnostics side that using nucleosome fragmentation pattern mapping of cell-free DNA instead of sequence variations, scientists could identify where a tumor originated, for use in situations not typically detected by traditional liquid biopsies. We know the interplay of oncogenes “being turned on” and tumor suppressor genes “being turned off”. We’ve mapped The Cancer Genome Atlas (TGCA) and determined probable-cause risk factors in radiation (e.g. UV in sunlight), viruses (e.g. HPV), and both endogenous and exogenous chemicals causing mutations both chemically and mechanistically (e.g. asbestos). Targeted therapies are aimed at the ~200 genes common throughout various cancers, using synergistically combined products and conjugates, and 12 pathways that regulate three core cellular processes across all cancer, e.g. cell fate, cell survival, and genome maintenance.
The Public Broadcasting System documentary series Cancer: The Emperor of All Maladies begins with a focus on early treatments that continue today, so-called “Magic Bullets” of surgery (beginning with the disfiguring radical mastectomies of the early 20th century that continued as a main course of treatment until a groundbreaking 1985 study), radiation, and chemotherapeutics. Based on the book of the same name by Siddhartha Mukherjee, MD, that won the 2011 Pulitzer Prize for General Non-Fiction, it traces cancer’s history, taboo, and patient impact, plus many therapies. One of my favorite authors, Malcolm Gladwell, who always seems to have a talent for extrapolative analytic-then-predictive writing, revealed with a bit more intimacy the early days and “superstars” of the National Cancer Institute (NCI), namely Emil Freireich, Tom Frei, and Vincent DeVita, Jr. DeVita’s book “The Death of Cancer”, co-authored with Elizabeth DeVita-Raeburn, chronicles his work on Hodgkin lymphoma, the disease that killed the husband of a previous employer of mine. In this article for the New Yorker in December, Gladwell contrasts “The Emperor of All Maladies” and “The Death of Cancer”, where the first is “a social and scientific biography of the disease” and the latter is “institutional history of the war on cancer”, specifically an “angry book, in which one of the critical figures in twentieth-century oncology unloads a lifetime of frustration”. For those interested in oncology and oncology therapeutics, I’d say the two offer that much more of a complete picture. While one celebrates how far we’ve come, and the other touches on the very complaints patients themselves make over healthcare and its progress, both show the bioethics of the “art of practicing medicine”, “innovation” versus “recklessness”, emotionally-driven patient advocacy versus scientific and quality rigor, and legal off-label prescribing in the U.S. based on prescriber’s judgment.
Although we can certainly argue the point that we have come far technically, have we really come so far ethically from the sometimes vertigo-inducing freewheeling of The Knick? Where, as Gladwell puts it: “Life on the innovation end of the continuum is volatile, fractious, and personal—less a genteel cocktail party, governed benignly by bureaucratic fiat, than the raucous bender where your boss passes out in a bathtub.” I actually like to imagine pure science like that – a frenetic, euphoric bender of creativity- but with the morning-after embracing that we have people to answer to and we have people we care about. In addition to therapies to fight cancer, additional focus has been on prevention, public health messages, and behavior modification targeted at the individual. The focus on the individual speaks to 2016 as the Year of Personalized Medicine, including cancer treatment. Some say we may be in a Golden Age of cancer research and therapeutic development. However, we must acknowledge that until cancer’s diseases are eradicated, we will have to speak to the practice of care for the dying as does Atul Gawande, MD, in his book and subsequent FRONTLINE documentary Being Mortal.
February 4th was World Cancer Day 2016 in collaboration with many corporate partners and supporters, e.g., Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Amgen, and Roche, along with the World Cancer Research Fund. The theme for this year that emphasizes the beginning of a 2016-2018 collective and individual empowerment campaign is: “We can. I can.” We can all take measures of prevention. We can support innovation and science in the public, to in turn support a societal culture that promotes knowledge, medical development, and healing. We can support others and ourselves. Recalling from the beginning of my speaking with you here: scientists, doctors, researchers, nurses, administrative and regulatory personnel, and legislators… all of us are touched by cancer. We all have personal stakes in this.
Image credit: pixabay