Reverting to single-cell biology: The predictions of the atavism theory of cancer.

Abstract Cancer or cancer-like phenomena pervade multicellular life, implying deep evolutionary roots. Many of the hallmarks of cancer recapitulate unicellular modalities, suggesting that cancer initiation and progression represent a systematic reversion to simpler ancestral phenotypes in response to a stress or insult. This so-called atavism theory may be tested using phylostratigraphy, which can be used to assign ages to genes. Several research groups have confirmed that cancer cells tend to over-express evolutionary older genes, and rewire the architecture linking unicellular and multicellular gene networks. In addition, some of the elevated mutation rate – a well-known hallmark of cancer – is actually self-inflicted, driven by genes found to be homologs of the ancient SOS genes activated in stressed bacteria, and employed to evolve biological workarounds. These findings have obvious implications for therapy.