Convergent Therapeutic Strategies to Overcome the Heterogeneity of Acquired Resistance in BRAF^V600E Colorectal Cancer.

ABSTRACT: Clonal heterogeneity associated with acquired resistance presents a critical therapeutic challenge. Whole-exome sequencing of paired tumor biopsies and targeted sequencing of cell-free DNA (cfDNA) from patients with BRAF^V600E colorectal cancer receiving BRAF inhibitor combinations identified 14 distinct alterations in MAPK pathway components driving acquired resistance, with as many as eight alterations in a single patient. We developed a pooled clone system to study clonal outgrowth during acquired resistance, in vitro and in vivoIn vitro, the dynamics of individual resistant clones could be monitored in real time in cfDNA isolated from culture media during therapy. Outgrowth of multiple resistant clones was observed during therapy with BRAF, EGFR, a

SUBMITTER: Hazar-Rethinam M 

PROVIDER: S-EPMC5882515 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature