Format

Send to

Choose Destination
Phys Biol. 2012 Dec;9(6):065007. doi: 10.1088/1478-3975/9/6/065007. Epub 2012 Nov 29.

Cancer treatment as a game: integrating evolutionary game theory into the optimal control of chemotherapy.

Author information

1
Biometry Research Group, Division of Cancer Prevention, National Cancer Institute,Executive Plaza North, Suite 3131, 6130 Executive Blvd, MSC 7354, Rockville, MD 20852, USA. paul.orlando@nih.gov

Abstract

Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors 'choose' an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor 'chooses' its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients.

PMID:
23197192
PMCID:
PMC3653600
DOI:
10.1088/1478-3975/9/6/065007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for IOP Publishing Ltd. Icon for PubMed Central
Loading ...
Support Center