Evolutionary dynamics of cancer in response to targeted combination therapy
View/ Open
Author
Reiter, Johannes G
Antal, Tibor
Chatterjee, Krishnendu
Shah, Preya
Yaqubie, Amin
Kelly, Nicole
Le, Dung T
Lipson, Evan J
Chapman, Paul B
Diaz, Luis A
Vogelstein, Bert
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.7554/eLife.00747Metadata
Show full item recordCitation
Bozic, I., J. G. Reiter, B. Allen, T. Antal, K. Chatterjee, P. Shah, Y. S. Moon, et al. 2013. “Evolutionary dynamics of cancer in response to targeted combination therapy.” eLife 2 (1): e00747. doi:10.7554/eLife.00747. http://dx.doi.org/10.7554/eLife.00747.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.00747.001Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691570/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11708553
Collections
- FAS Scholarly Articles [18256]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)