BRAF encodes a serine/threonine kinase that transduces mitogenic signals from the cell membrane to the nucleus by phosphorylating MAP2K1, thereby activating the MAPK signaling cascade. It also phosphorylates PFKFB2 and may contribute to postsynaptic signaling in hippocampal neurons. Oncogenic BRAF mutations, particularly the V600E variant present in approximately 40% of metastatic melanomas, constitutively activate MAPK signaling and drive malignant transformation across multiple cancer types. BRAF V600E mutations occur at 66% frequency in melanoma, 3% in non-small cell lung carcinoma, and smaller percentages in pancreatic cancer and other malignancies 1. Non-V600 BRAF mutations represent nearly 35% of all BRAF mutations in cancer and exhibit distinct functional and therapeutic profiles 2. BRAF mutations also associate with developmental disorders including cardiofaciocutaneous syndrome and Costello syndrome. Multiple selective BRAF inhibitors including dabrafenib, encorafenib, sorafenib, and plixorafenib have been developed to target oncogenic BRAF variants. In June 2022, the FDA granted accelerated approval to dabrafenib combined with the MEK inhibitor trametinib for unresectable or metastatic BRAF V600E-mutant solid tumors, except colorectal cancers 3. Encorafenib and binimetinib combination therapy received FDA approval in 2018 for BRAF V600E/K-mutated melanoma 4. However, resistance develops in most patients, necessitating combination strategies and novel therapeutic approaches to extend treatment benefit.