Evolutionary dynamics of cancer in response to targeted combination therapy Journal Article


Author(s): Božić, Ivana; Reiter, Johannes G; Allen, Benjamin; Antal, Tibor; Chatterjee, Krishnendu; Shah, Preya; Moon, Yo Sup; Yaqubie, Amin; Kelly, Nicole; Le, Dung T; Lipson, Evan J; Chapman, Paul B; Diaz, Luis A; Vogelstein, Bert; Nowak, Martin A
Article Title: Evolutionary dynamics of cancer in response to targeted combination therapy
Affiliation IST Austria
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.
Journal Title: eLife
Volume: 2
ISSN: 2050-084X
Publisher: eLife Sciences Publications  
Date Published: 2013-06-25
Start Page: e00747
Copyright Statement: CC BY
URL:
DOI: 10.7554/eLife.00747
Open access: yes (OA journal)