Exploiting evolutionary steering to induce collateral drug sensitivity in cancer.

ABSTRACT: Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 10⁸-10⁹ cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model

SUBMITTER: Acar A 

PROVIDER: S-EPMC7174377 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature