Paradoxes in Carcinogenesis Should Spur New Avenues of Research: An Historical Perspective

A major obstacle to winning the war on cancer is a lack of understanding of how cancer develops. The dominant theory for the last 50 years has been the somatic mutation theory (SMT), which says that cancer arises directly from a sequence of genetic changes on a cell that leads to its proliferation. The alternative tissue organization field theory (TOFT) says that cancers arise from a disruption of cell communication needed to maintain normal tissue architecture. A historical background places these theories into perspective. Various experimental results are paradoxical under SMT, but readily explained under TOFT, suggesting paradigm instability. These paradoxical results offer new opportunities for cancer research.