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Cancer: More of polygenic disease and less of multiple mutations? A quantitative viewpoint†
Article first published online: 22 SEP 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 3, pages 440–445, 1 February 2011
How to Cite
Bredberg, A. (2011), Cancer: More of polygenic disease and less of multiple mutations? A quantitative viewpoint. Cancer, 117: 440–445. doi: 10.1002/cncr.25440
I thank Jenny Liao-Persson, Ake Larsson and Aida Gabdoulkhakova for their critical reading of this text and for valuable suggestions.
- Issue published online: 20 JAN 2011
- Article first published online: 22 SEP 2010
- Manuscript Revised: 21 APR 2010
- Manuscript Accepted: 21 APR 2010
- Manuscript Received: 19 FEB 2010
- cancer resistance;
- targeted therapy;
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.