Resistance to BRAF inhibition explored through single circulating tumour cell molecular profiling in BRAF-mutant non-small-cell lung cancer.

ABSTRACT:

Background

Resistance mechanisms to combination therapy with dabrafenib plus trametinib remain poorly understood in patients with BRAF^V600E-mutant advanced non-small-cell lung cancer (NSCLC). We examined resistance to BRAF inhibition by single CTC sequencing in BRAF^V600E-mutant NSCLC.

Methods

CTCs and cfDNA were examined in seven BRAF^V600E-mutant NSCLC patients at failure to treatment. Matched tumour tissue was available for four patients. Single CTCs were isolated by fluorescence-activated cell sorting following enrichment and immunofluorescence (Hoechst 33342/CD45/pan-cytokeratins) and sequenced for mutation and copy number-alteration (CNA) analyses.

Results

BRAF^V600E was found in 4/4 tumour biopsies and 5/7 cfDNA samples.

SUBMITTER: Mezquita L 

PROVIDER: S-EPMC10876548 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature