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  • Somatic evolution of Cancer...
    Baig, Ulfat; Kharate, Rohini; Watve, Milind

    Qeios, 11/2023
    Journal Article

    Out of the multiple interpretations of cancers, two predominant ones have been (i) somatic evolution of cheater cells that escape replication regulation and (ii) cancers as non-healing wounds. Both the interpretations have substantial support as well as glaring anomalies but the two along with other possible interpretations have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve _de novo_. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any _de novo_ gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective challenges multiple prevalent ideas, suggests novel lines of research and also has translatable implications for cancer prevention.