The secretome features associated with the development of re-sistance to vemurafenib in BRAFV600E mutated colon cancer cells

Patients with metastatic colorectal cancer (mCRC) carrying BRAFV600E mutation have worse response to chemotherapy and poor prognosis. The aim of this study was to conduct for the first time comparative proteomics profiling of the secretome from vemurafenib-sensitive vs. resistant colon cancer cells harboring BRAFV600E mutation in order to identify specific secretory features potentially associated with the development of resistance to vemurafenib. Towards this aim, we employed a label-free quantitative LC-MS/MS analysis. Obtained results pointed to aberrant regulation of DNA replication and the endoplasmic reticulum stress as the major secretome features associated with chemoresistant phenotype. Further studies are required to investigate diagnostic values of these proteins in the clinical setting and to examine their roles in acquired resistance to BRAF inhibition not only in colon cancer but also in other BRAF mutated cancers.