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Elife. 2013 Jun 25;2:e00747. doi: 10.7554/eLife.00747.

Evolutionary dynamics of cancer in response to targeted combination therapy.

Author information

1
Program for Evolutionary Dynamics , Harvard University , Cambridge , United States ; Department of Mathematics , Harvard University , Cambridge , United States.

Abstract

In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics. DOI:http://dx.doi.org/10.7554/eLife.00747.001.

KEYWORDS:

None; cancer; genetics; mathematical biology; stochastic processes; targeted therapy

PMID:
23805382
PMCID:
PMC3691570
DOI:
10.7554/eLife.00747
[Indexed for MEDLINE]
Free PMC Article
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