define the series of tests required for validation and confirmation of findings in order to ensure that interventions are warranted. For example, if circulating tumor cells are identified in an otherwise healthy individual, a supplemental CT or PET scan may reveal the precise origin of the cancer. If the tumor is not yet detectable by existing imaging, however, are there other biomarkers that would prove useful to identify the tissue of origin? Single-cell simultaneous sequencing of RNA and DNA is already developed and could detect “cancers of unknown primary” with even greater precision. In what order should these further tests be conducted?
Education to generate a broad coalition with a clear call to action: Success for any such paradigm shift requires meaningful education at every level from patients and families to the treating oncologists to the cancer research communities and ultimately to the public. There must be clear explanations of why a change is urgently needed, as well as models showing how success will dramatically lessen cancer’s impact on the world and how such sweeping programs can democratize health care by removing inequalities. National societies focused on cancer such as the American Society of Clinical Oncology, the American Association for Cancer Research and the American Society of Hematology already have the platforms including annual meetings, publications and outreach programs to facilitate the education of all stakeholders.
Interdisciplinary studies must be implemented, formally combining research in oncology with cutting-edge research in evolutionary biology, physics, computational biology, machine learning and artificial intelligence dedicated to following the natural history starting with wellness to disease to progression. Such studies should not be limited to humans because there are many examples in nature where species are protected from developing cancer (e.g., elephants, blue whales), and a formal discipline dedicated to the comparative study of cancers across species could be critical in developing preventive measures eventually.
One strategy for the implementation of such a broad and far-reaching program would be to embark on the systems approach targeting a group at high risk of developing cancer—notably cancer survivors. Of 1.7 million cancers diagnosed annually in the U.S., one in five arise in a cancer survivor. There are currently 16.9 million cancer survivors, and the number will increase to 26 million by 2040. Practically every major institution caring for cancer patients has a large population of cancer survivors coming regularly for periodic checkups. Resources should be dedicated to obtaining multiple tissues such as blood, urine, saliva and stools periodically from cancer survivors to identify markers for, and develop insights into, their wellness-to-recurrence transitions.
Expanding the scope of large-scale noninvasive projects and encouraging health care systems and academic centers to establish biobanks with
multiple specimens collected from every individual who walks through their door, will create a rich resource that can change the current paradigm of cancer health care with deliberate speed.
TOTT acknowledges that a high proportion of cancers arising in survivors will be relapses of already highly complex malignant cell populations, and that these will be fundamentally different from those neoplasms emerging de novo in a stepwise fashion. We also understand that the biomarkers detected in second primary cancers in this high-risk group are unlikely to be the same as those found in first-time cancer patients. But their detection would provide proof of principle for the wellness-to-disease transition model, and add to the knowledge needed for broadening this approach to elevated-genetic-risk segments of the healthy population.
As Thomas Kuhn famously pointed out in his book The Structure of Scientific Revolutions,“Paradigms gain their status because they are more successful than their competitors in solving a few problems that the group of practitioners has come to recognize as acute.” Cancer survivors may provide such a successful opportunity, and hopefully, the results will be lifesaving not just for cancer survivors but for everyone.
The co-authors of this essay are listed below. If not otherwise noted, they have indicated that they have no potential conflicts of interest.
Azra Raza, M.D., is a professor of medicine at the Columbia University Irving Medical Center (CUIMC). She has received grants from GRAIL and Regeneron Pharmaceuticals.
Abdullah M. Ali, Ph.D., is a research scientist at CUIMC. He has no potential conflicts directly related to this work. Outside of it, Ali is currently in receipt of grants from GRAIL, Tolero Pharmaceuticals and Regeneron. He is also a consultant to Vor Biopharma.
Aris Baras, M.D., M.B.A., is senior vice president of Regeneron and founder and general manager of the Regeneron Genetics Center, a wholly owned subsidiary of Regeneron. He is an employee of Regeneron and owns stock in the company.
Robert Gallo, M.D., is a professor of medicine and director of the Institute of Human Virology at the University of Maryland School of Medicine.
Robert A. Gatenby, M.D., is a senior member at the Moffitt Cancer Center.
Anisa Hassan, M.D., H.M.D.C., is a hematologist-oncologist staff physician at Freeman Health System.
Mark L. Heaney, M.D., is an associate professor of medicine at CUIMC.
Joseph G. Jurcic, M.D., is a professor of medicine at CUIMC. He has no potential conflicts directly related to this work. Outside of it, Jurcic receives research funding paid to Columbia University from AbbVie, Arog Pharmaceuticals, Astellas Pharma, Celgene, Daiichi Sankyo, Forma Therapeutics, Genentech, Kura Oncology, PTC Therapeutics and Syros Pharmaceuticals. He has consulted for or serves on advisory boards for AbbVie, Actinium Pharmaceuticals and Novartis.
Stavroula Kousteni, Ph.D., is a professor of physiology and cellular biophysics at CUIMC.
Richard Larson, M.D., is a professor of medicine at the University of Chicago. He has acted as a consultant or adviser to Agios, Amgen, Ariad Pharmaceuticals/Takeda Pharmaceutical Company, Astellas Pharma, Celgene/Bristol-Myers Squibb, CVS Caremark, Epizyme, MorphoSys and Novartis. And he has received clinical research support from Astellas, Celgene, Cellectis, Daiichi Sankyo, Forty Seven, Gilead Sciences, Novartis and Rafael Pharmaceuticals, as well as royalties from UpToDate.
Frank Laukien, Ph.D., is president and CEO of Bruker Corporation, as well as a shareholder of the company. Bruker is a Nasdaq-traded life-science tools company that makes and sells scientific instruments, which can also be used for cancer research, among many other uses and applications. Cancer research tools represent less than 1 percent of Bruker’s revenue.
Steven H. Lin, M.D., Ph.D., is an associate professor of radiation oncology at the University of Texas MD Anderson Cancer Center. He has received grants from BeyondSpring and Hitachi Chemical Diagnostics. And he serves on advisory boards for STCube, BeyondSpring and AstraZeneca.
Guido Marcucci, M.D., is a professor of medicine at City of Hope National Medical Center.
Jayesh Mehta, M.D., is a professor of medicine at Northwestern University’s Feinberg School of Medicine.
Siddhartha Mukherjee, M.D., Ph.D., is an associate professor of medicine at CUIMC.
Joshua Ofman, M.D., is chief medical officer at GRAIL and is an equity owner of the company.
Patrizia Paterlini, M.D., Ph.D., is a professor of oncology at University Paris Descartes and a founder and shareholder of Rarecells; the company is the exclusive licensee of the ISET patents, which Paterlini co-invented.
Kenneth Pienta, M.D., is a professor of urology, oncology, and pharmacology and molecular sciences at the Johns Hopkins School of Medicine. He is a consultant for Cue Biopharma.
Samuel Sia, Ph.D., is a professor of biomedical engineering at Columbia University and co-founder of Rover Diagnostics.
Seema Singhal, M.D., is a professor of medicine at Northwestern University’s Feinberg School of Medicine.
B. Douglas Smith, M.D., is a professor of oncology at the Johns Hopkins School of Medicine.
Patrick Soon-Shiong, M.D., is executive chairman of ImmunityBio; adjunct professor of surgery at the University of California, Los Angeles; visiting professor at Imperial College London; and executive chairman of the Los Angeles Times.
David P. Steensma, M.D., is an associate professor of medicine at the Dana-Farber Cancer Institute. He has no conflict-of-interest disclosures directly related to this work. Steensma acts as a consultant for Pfizer, Cellarity, Taiho, Onconova Therapeutics and Celgene/Bristol-Meyers Squibb.
John Wrangle, M.D., is an associate professor of medicine at the Medical University of South Carolina.
Leroy Hood, M.D., Ph.D., is Senior Vice President and Chief Science Officer at Providence St. Joseph Health.
https://www.scientificamerican.com/article/we-must-find-ways-to-detect-cancer-much-earlier/
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