We found that the combination of avutometinib + defactinib (or the combination of avutometinib and the FAKi VS-4718 used as a surrogate for defactinib in preclinical studies) showed strong activity against a variety of Rac1-driven BRAFi-resistant melanoma cell lines in vitro under both 2D (Figs. 7A–J) and 3D growth conditions (Fig. 7K, L). The gene discussed is RAC1; the disease is melanoma.