The Targeted Degradation of BRAF V600E Reveals the Mechanisms of Resistance to BRAF-Targeted Treatments in Colorectal Cancer Cells.

ABSTRACT: The BRAF V600E mutation is frequently found in cancer. It activates the MAPK pathway and promotes cancer cell proliferation, making BRAF an excellent target for anti-cancer therapy. While BRAF-targeted therapy is highly effective for melanoma, it is often ineffective against other cancers harboring the BRAF mutation. In this study, we evaluate the effectiveness of a proteolysis targeting chimera (PROTAC), SJF-0628, in directing the degradation of mutated BRAF across a diverse panel of cancer cells and determine how these cells respond to the degradation. SJF-0628 treatment results in the degradation of BRAF V600E and a decrease in Mek activation in all cell lines tested, but the effects of the treatment on cell signaling and cell proliferation are cell-line-specific. First, B

SUBMITTER: Chapdelaine AG 

PROVIDER: S-EPMC10741866 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature