• cancer;
  • cancer resistance;
  • targeted therapy;
  • carcinogenesis;
  • prevention


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.