3D structure of a melanoma cell derived by ion abrasion scanning electron microscopy. Credit: National Cancer Institute, Unsplash (CC0, creativecommons.org/publicdomain/zero/1.0/)
March 18, 2025
It's time for researchers to reconsider the current paradigm of cancer as a genetic disease, argues Sui Huang from the Institute for Systems Biology, U.S., and colleagues in an essay published in the open-access journal PLOS Biology.
The prevailing theory on the origin of cancer is that an otherwise normal cell accumulates genetic mutations that allow it to grow and reproduce unchecked. This paradigm has driven large-scale cancer genome sequencing projects, such as The Cancer Genome Atlas, to identify cancer-driver mutations and develop drugs designed to target aberrant proteins and pathways.
In their new essay, Huang and colleagues argue that this somatic mutation theory of cancer is unproductive. They point to inconsistencies in the sequencing data that contradict the current theory, including the fact that many cancers have no known driver mutations while some normal tissues can harbor cancer-causing mutations.
They propose a broader, more "holistic" view that embraces organismal biology and theory. Specifically, they encourage considering alternative paradigms that encompass non-genetic processes involved in tumorigenesis. For example, they explain the concepts of cancer as a result of disruptions in gene regulatory networks—or of tissue organization, a theory that considers the disturbance of the field generated by neighboring cells and surrounding tissue.
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