Wnt5A and ROR2 contribute to intrinsic resistance to BRAF inhibitors. Wnt5A and ROR2 contribute to intrinsic resistance to BRAF inhibitors. A, Wnt5A and (C) ROR2 mRNA levels in sensitive and resistant melanoma cell lines analyzed by RT-PCR (P < 0.05 and P < 0.005, respectively). B, PLX-sensitive 451LU melanoma cells were treated with increasing doses of PLX4720 and proliferation was analyzed by an MTS assay. D, PLX-resistant 1205LU cells were transfected with CTRL or ROR2 siRNA, and were then treated with increasing doses of PLX4720. E, tumor volume analysis in athymic nude mice injected with 1205LU cells transfected with CTRL or ROR2 siRNA. Once tumor formation had occurred (∼200 mm3), mice were fed either control AIN-76A chow or AIN-76A chow containing 417 mg/kg PLX4720, and tumors were tracked for 16 days. The percentage change in tumor volume was recorded. F, ROR1 mRNA levels in sensitive and resistant melanoma cell lines analyzed by RT-PCR (P < 0.005). G, tumor volume analysis in athymic nude mice injected with WM35 cells transfected with CTRL or ROR1 siRNA. Once tumor formation had occurred, mice were fed either control AIN-76A chow or AIN-76A chow containing 417 mg/kg PLX4720 and tumors were tracked for 21 days. The change in tumor volume was recorded. Michael P. O'Connell et al. Cancer Discovery 2013;3:1378-1393 ©2013 by American Association for Cancer Research