Laura J Jenkins, Ian Y Luk, Fiona Chionh, Tao Tan, Kristen Needham, Jamieson Ayton, Camilla M Reehorst, Natalia Vukelic, Oliver M Sieber, Dmitri Mouradov, Peter Gibbs, David S Williams, Niall C Tebbutt, Jayesh Desai, Frédéric Hollande, Amardeep S Dhillon, Erinna F Lee, Delphine Merino, W Douglas Fairlie, John M Mariadason
Metastatic BRAFV600E colorectal cancer (CRC) carries an extremely poor prognosis and is in urgent need of effective new treatments. While the BRAFV600E inhibitor encorafenib in combination with the EGFR inhibitor cetuximab (Enc+Cet) was recently approved for this indication, overall survival is only increased by 3.6 months and objective responses are observed in only 20% of patients. We have found that a limitation of Enc+Cet treatment is the failure to efficiently induce apoptosis in BRAFV600E CRCs, despite inducing expression of the pro-apoptotic protein BIM and repressing expression of the pro-survival protein MCL-1...
March 1, 2024: Cell Death & Disease