EGFR and head and neck cancer: In addition, crosstalk between AXL and HER3 promotes invasion and metastatic progression in melanoma cells by regulating invadopodia formation.205 In NSCLC, AXL interacts with HER3 with EGFR within a negative feedback system involving SPRY4, resulting in resistance to the EGFR inhibitor osimertinib.222,228 In head and neck cancer, AXL mediates cetuximab resistance through two mechanisms: activation of c-ABL kinase via AXL’s Y821 phosphorylation229 and HER3 activation due to upregulated NRG1.31