Author(s): Wyatt Legas, Reno Blackmore, Jacob Mead
Mentor(s): Jennifer Meyer
Institution UTech
Melanoma, the deadliest form of skin cancer, is driven by a V600E BRAF mutation in nearly 60% of cases. Dabrafenib is a standard treatment for patients with this mutation; however, resistance frequently develops within months of initiation. This study aims to enhance dabrafenib's therapeutic efficacy by pairing it with pterostilbene, a naturally occurring compound with anti-cancer properties, using the A375 melanoma cell line. Once IC50 values were determined for each drug, isobologram analysis determined a synergistic relationship between dabrafenib and pterostilbene at five concentration combinations. Moreover, western blotting revealed that the combined treatment significantly reduced phospho-ERK levels compared to either drug alone. Present efforts focus on the protein expression involved in apoptosis, as well as expanding to an additional cell line, HT-144, which also harbors the BRAF mutation. Current results indicate the combination of dabrafenib and pterostilbene effectively disrupts key signaling pathways, suggesting a promising strategy to reduce cell viability in cancers containing the V600E BRAF mutation.. Continued research with HT-144 cells and detailed protein expression analysis aims to validate these results, potentially leading to more effective treatments that reduce resistance and improve patient outcomes.