Therapeutic resistance and susceptibility is shaped by cooperative multi-compartment tumor adaptation.

ABSTRACT: Emerging research suggests that multiple tumor compartments can influence treatment responsiveness and relapse, yet the search for therapeutic resistance mechanisms remains largely focused on acquired genomic alterations in cancer cells. Here we show how treatment-induced changes occur in multiple tumor compartments during tumor relapse and can reduce benefit of follow-on therapies. By using serial biopsies, next-generation sequencing, and single-cell transcriptomics, we tracked the evolution of multiple cellular compartments within individual lesions during first-line treatment response, relapse, and second-line therapeutic interventions in an autochthonous model of melanoma. We discovered that although treatment-relapsed tumors remained genetically stable, they converged on a shared resi

SUBMITTER: Long JE 

PROVIDER: S-EPMC6889278 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature