<p>In this study, we evaluated the clinical efficacy of combined <a href="https://www.ncbi.nlm.nih.gov/gene/5133">PDCD1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/673">BRAF</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/5609">MAP2K7</a> inhibition in metastatic BRAFV600E Colorectal Cancer (CRC) patients (<a href="https://clinicaltrials.gov/ct2/show/NCT03668431">NCT03668431</a>). We performed bulk whole exome sequencing (WXS) and bulk RNA sequencing (RNA-Seq) in 35 pre-treatment tumor biopsies and matching germline for tumor mutational burden (TMB), BM1/BM2 transcriptional subtypes, and consensus molecular subtypes (CMS) analysis, which were previously reported to affect prognosis and response to therapy (PMIDs: <a href="https://pubmed.ncbi.nlm.nih.gov/32047001/">32047001</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/27354468/">27354468</a>, and <a href="https://pubmed.ncbi.nlm.nih.gov/26457756/">26457756</a>). Analysis of bulk data showed that TMB, BM1/BM2 subtypes, and CMS did not correlate with clinical response in this study. Analysis of single cell RNA sequencing (scRNA-Seq) data of tumor epithelial cells from 23 paired day 0 and day 15 tumor biopsies revealed greater induction of tumor cell-intrinsic immune programs and more complete MAPK inhibition in patients with better clinical outcome.</p>

Combined PDCD1, BRAF and MAP2K7 Inhibition in BRAFV600E Colorectal Cancer: A Phase 2 Trial

Description

Applying For Access

Summary