Intratumor heterogeneity alters most effective drugs in designed combinations.

ABSTRACT: The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributio

SUBMITTER: Zhao B 

PROVIDER: S-EPMC4115561 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature