title: Molecular theory of cancer.
abstract: The mutation theory of cancer was always confronted by alternative (vitalistic) theories, which insist that cancer (like life itself) cannot be reduced to molecular interactions. In fact, the most fundamental feature of the somatic mutation theory of cancer is that it is a molecular theory, meaning that all the complexity of cancer on any level (e.g., tissue) can be explained on the molecular level. To emphasize the essence of mutation theory, cancer-causing mutation can be defined as any (a) molecular event that is (b) somatically inheritable and (c) selectable (e.g., provides selective advantage in restrictive/carcinogenic conditions). Here I review molecular (somatic mutation) theory and its alternatives and discuss that molecular interactions can completely explain complex tissue phenomena such as benign tumors and stroma initiated tumorigenesis. In addition, molecular theory predicts extragenetic somatic hereditary in cancer (e.g., posttranslational protein modifications that initiate and are supported by positive feedback loops) and also explains the relationship between selection for resistance, hallmarks of cancer and genetic instability. From molecules to cells to the organism, this review discusses how somatically heritable molecular alterations (genetic, epigenetic and extragenetic) alter translation of cellular signals, resulting in resistance to growth inhibition and apoptosis, that is manifested as secondary hallmarks of cancer (metastasis, angiogenesis and immortality) and, finally, as the amazing ability of some cancer cells such as canine transmissible sarcoma to 'live in a wild' like unicellular mammalian species.
authors.affiliation: Cancer Center, Ordway Research Institute, Albany, New York 12208, USA. blagosklonny@oncotarget.com
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
mesh_terms: D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*