ROS1 and lung carcinoma: In renal cancer, prolonged sunitinib treatment increases c-MET and AXL expression, leading to acquired resistance against sunitinib, which can be countered with cabozantinib.256 Similarly, cabozantinib combined with gefitinib has been effective in countering resistance to crizotinib and ROS1-TKIs in lung cancers with ROS1 fusions, where active HB-EGF/EGFR and AXL signaling contribute to resistance.257