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Cancer. 2011 Feb 1;117(3):440-5. doi: 10.1002/cncr.25440. Epub 2010 Sep 22.

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

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1
Department of Laboratory Medicine, Skane University Hospital, Lund University, Malmo, Sweden. anders.bredberg@med.lu.se

Abstract

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.

PMID:
20862743
DOI:
10.1002/cncr.25440
[Indexed for MEDLINE]
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