Oncotarget: Paradox breaker BRAF inhibitors in BRAF mutant colorectal cancer

 Oncotarget Volume 11, Issue 34 features Figure 1, "BRAF inhibitor-induced changes in cell viability," by Pickles, et which reported that the BEACON CRC trial demonstrated a survival advantage over chemotherapy for a combination of targeted agents comprising the potent BRAF inhibitor encorafenib together with cetuximab and binimetinib.

Resistance to BRAF inhibition in CRC arises in part through the generation and activation of RAF dimers resulting in MEK-ERK pathway reactivation.

The Oncotarget authors analyzed whether paradox breakers reduce pathway reactivation and so have enhanced potency compared with encorafenib in BRAF mutant CRC.

However, dose-response curves for encorafenib and PLX8394 were similar and there were no significant differences in the degree of pathway reactivation.

To their knowledge, these data represent the first comparative data of encorafenib and paradox breaker inhibitors in BRAF mutant CRC.

Dr. Gary W. Middleton from The Institute of Immunology and Immunotherapy at The University of Birmingham said, "Around 10% of patients with metastatic colorectal cancer (CRC) harbour a BRAF mutation."