Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations.

ABSTRACT: Recent drug discovery and development efforts have created a large arsenal of targeted and chemotherapeutic drugs for precision medicine. However, drug resistance remains a major challenge as minor pre-existing resistant subpopulations are often found to be enriched at relapse. Current drug design has been heavily focused on initial efficacy, and we do not fully understand the effects of drug selective pressure on long-term drug resistance potential. Using a minimal two-population model, taking into account subpopulation proportions and growth/kill rates, we modeled long-term drug treatment and performed parameter sweeps to analyze the effects of each parameter on therapeutic efficacy. We found that drugs with the same overall initial kill may exert differential selective pressures, affect

SUBMITTER: Sun D 

PROVIDER: S-EPMC5098152 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature