Cancer: More of polygenic disease and less of multiple mutations? A quantitative viewpoint

The focus of cancer research is on cancer‐specific mutations, with most clinical trials involving targeted drugs. Huge numbers of DNA lesions and tumor resistance events, in each of the >10¹³ cells of a human individual, form a striking contrast to the low, and also very narrow, cancer incidence window (10^?1‐10⁰). A detailed consideration of these quantitative observations seems to question the present paradigm, while suggesting that a systemic regulatory network mechanism is a stronger determinant for overt cancer disease, as compared with cancer‐specific gene products. If we shall ever achieve major improvements in survival, we must gain understanding of this systemic network, rather than targeting therapy to a limited set of molecules or mutations. This may give us new opportunities for development of highly potent therapeutic tools. Cancer 2011. © 2010 American Cancer Society.