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.
Bredberg
Anders
A
Department of Laboratory Medicine, Skane University Hospital, Lund University, Malmo, Sweden. anders.bredberg@med.lu.se
D004198:Disease Susceptibility; D016503:Drug Delivery Systems; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control*