Evolutionary dynamics of cancer in response to targeted combination therapy

Bozic, Ivana and Reiter, Johannes G and Allen, Benjamin and Antal, Tibor and Chatterjee, Krishnendu and Shah, Preya and Moon, Yo Sup and Yaqubie, Amin and Kelly, Nicole and Le, Dung T and Lipson, Evan J and Chapman, Paul B and Diaz, Luis A and Vogelstein, Bert and Nowak, Martin A (2013) Evolutionary dynamics of cancer in response to targeted combination therapy. eLife, 2. Article Nr. e00747. ISSN 2050-084X

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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.

Item Type: Article
DOI: 10.7554/eLife.00747
Subjects: 500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine and health
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 17 Jul 2013 08:42
Last Modified: 30 Aug 2017 09:48
URI: https://repository.ist.ac.at/id/eprint/134

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