BRAF and melanoma: In vitro studies evaluating the pathophysiology of acquired resistance to combination therapy have shown that resistant melanoma cell lines exhibit a much greater degree of drug addiction than cell lines resistant to BRAF inhibitors alone.66 Similar to what has been observed in tumors of patients who progressed on a single BRAF inhibitor and were then treated with BRAF and MEK inhibitors, BRAF inhibitor-resistant cell lines demonstrated the ability to rapidly adapt to combination therapy.