Many patients treated for metastatic melanoma develop resistance to an otherwise effective drug therapy known as BRAF inhibitors, which targets a specific genetic mutation. The cause of this resistance in 40% of patients is unclear. Yale researchers identified a new protein that, when downregulated, can result in resistance to BRAF inhibitors.
The research team, led by Associate Professor of Pathology Narendra Wajapeyee, PhD and Associate Research Scientist of Pathology, Romi Gupta, PhD, first conducted a comprehensive screen of non-genetic factors in cancer cells that might affect drug resistance. They identified a protein, BOP1, that is decreased in expression in drug-resistant cells. While it is not clear why BOP1 expression is lost in these cells, Dr. Wajapeyee noted, the loss activates a molecular pathway that triggers resistance to BRAF inhibitor treatment.
This finding suggests that the addition of other drug therapies might counter resistance to BRAF inhibitors in melanoma patients. By targeting other proteins in cancer cells with existing therapies, researchers may be able to treat this aggressive cancer more effectively.
The full paper is published in PNAS.