Fig. 5
From: AXL signaling in cancer: from molecular insights to targeted therapies

AXL-directed therapeutic resistance via activation of bypass signaling. a Under basal conditions, AXL is shed through the action of ADAM10/17. b In bypass signaling, MAPK inhibition decreases sheddase activity by enhancing the association between TIMP1 and ADAM10/17. This inhibition boosts mitogenic signaling through bypass kinases like JNK, leading to sustained secondary tolerance to EGFR TKIs