In a recent essay, scientists challenge the prevailing genetic-focused model of cancer, advocating for a shift towards more holistic views that include non-genetic factors in cancer development.
They criticize the inconsistencies in current genetic research and propose considering alternative paradigms like disruptions in gene regulatory networks and tissue organization theories. This approach could lead to more effective cancer treatments and preventive measures against environmental non-mutagenic carcinogens.
Reevaluating Cancer Research
Researchers should reconsider the long-held belief that cancer is primarily a genetic disease, argues Sui Huang of the Institute for Systems Biology and colleagues in a newly published essay in PLOS Biology.
For decades, the dominant theory has been that cancer develops when a normal cell accumulates genetic mutations, allowing it to grow and multiply uncontrollably. This idea has fueled major genome sequencing projects like The Cancer Genome Atlas, aimed at identifying cancer-driving mutations and developing targeted treatments.
Challenging the Status Quo
However, Huang and his colleagues challenge this somatic mutation theory, calling it unproductive. They highlight inconsistencies in genetic data, such as cancers with no identifiable driver mutations and normal tissues that carry cancer-causing mutations without forming tumors.
Instead, they advocate for a broader, more holistic approach that considers biological systems beyond genetic mutations. They propose alternative models, including cancer as a disruption of gene regulatory networks (Huang) or as a breakdown in tissue organization, where disturbances in the cellular environment contribute to tumor development (Soto-Sonnenschein). According to the authors, exploring these alternative frameworks could lead to new insights into cancer’s origins and guide future research.
Beyond Genetic Mutations
The authors add: “A full embrace of the idea that the origin of cancer lies beyond the realm of genetic mutations will open new vistas on cancer treatment and prevention. Accepting that not all carcinogens are mutagens will strengthen public health policies aimed to prevent exposure to environmental non-mutagenic factors that may promote cancer, such as food additives and plastics and many other toxicants that alter tissue homeostasis.”
Reference: “The end of the genetic paradigm of cancer” by Sui Huang, Ana M. Soto and Carlos Sonnenschein, 18 March 2025, PLOS Biology.
DOI: 10.1371/journal.pbio.3003052
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4 Comments
“They propose alternative models, including cancer as a disruption of gene regulatory networks (Huang) or as a breakdown in tissue organization, where disturbances in the cellular environment contribute to tumor development…” I agree.
I am a medical anthropologist breast researcher and author, best known for my research into the link between breast cancer and the wearing of tight bras. I co-authored the book, Dressed to Kill. The cellular environment, or the extracellular matrix, is damaged by tight bras, and this impairs lymphatic drainage from the breasts. The lymphatic system is the circulatory pathway of the immune system, and is responsible for removing toxins from the tissues. Bra-caused compression and constriction of the breasts impairs the easily-compressed lymphatic system, and this results in fluid and toxin accumulation, breast pain and cysts, and ultimately can lead to cancer. See my article, How Bras Cause Lymph Stasis and Breast Cancer. https://theculturedoctor.substack.com/p/how-bras-cause-lymph-stasis-and-breast
For more references, see my website https://brasandbreastcancer.org/supportive-references
This idea is a decade late. Brucher and Jamali demolished the mutation theory in 2014 in their seminal article, “Epistemology of the origin of cancer: a new paradigm.” Accessed over 20,000 times and followed by some two dozen publications, “Epistemology . . .” has become a touchstone for many. Guess that neither the authors of the cited article nor the author of this “report” could be troubled to do their own literature search.
@Ray – Yes, there have been plenty of attempts to dismantle the mutation theory indeed, too numerous to quote them all. But this article summarizes all the MOST RECENT findings from hard gene sequencing data, notably next-generation deep sequencing and single-cells sequencing.
it is not expressing a general (albeit correct) sense that there is something fishy about a theory.
It is about fundamentals, not sentimentals.
@Ray. Yes, it is not unusual that relevant references are left not mentioned; we can give you some details on the subject. However, in this case, I respectfully submit that for instance, a 1962 beautiful paper by a certain David Smithers, published in a rather “popular” British medical journal (The Lancet) advocating against cytologism in cancer, went ignored. We resurrected it in our 1999 book THE SOCIETY OF CELLS and more recently in Acta Biotheoretica. Also, for those who early on were unable to read our book, in 2000, we published an article in MOLECULAR CARCINOGENESIS, with a rather provocative title for that time, in which we elaborated on the relevance of both the SMT and the TOFT. These references are included in our just published Essay in PLOS Biology. In addition to “deep thinking”, “deep reading” also helps in getting the big picture. As you probably know, there is a lot to be said and written about the sociology of cancer. Among others, Thomas Kuhn, also in 1962, made some comments on the subject of how new ideas are welcomed by us, scientists. CS & AMS