期刊
ELIFE
卷 2, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.00747
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资金
- Foundational Questions in Evolutionary Biology Fund
- European Research Council Start Grant [279307]
- FWF (The Austrian Science Fund) Grant [S11407-N23, P23499-N23]
- Microsoft Faculty Fellow Award
- John Templeton Foundation
- Danny Federici Melanoma Fund
- John Figge Melanoma Fund
- Virginia and D. K. Ludwig Fund for Cancer Research
- National Cancer Institute [N01-CN-43309]
- National Institutes of Health [CA129825, CA43460, CA57345]
- National Colorectal Cancer Research Alliance
- European Research Council (ERC) [279307] Funding Source: European Research Council (ERC)
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.
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