Ligand-Independent EPHA2 Signaling Drives the Adoption of a Targeted Therapy–Mediated Metastatic Melanoma Phenotype

摘要: Many patients with BRAF inhibitor resistance can develop disease at new sites, suggesting that drug-induced selection pressure drives metastasis. Here we used mass spectrometry-based phosphoproteomic screening to uncover ligand-independent EphA2 signaling as an adaptation therapy led the adoption of a metastatic phenotype. The EphA2-mediated invasion was AKT-dependent and readily reversible upon removal drug well through PI3K AKT inhibition. In xenograft models, inhibition development positive metastases. A retrospective analysis melanoma on showed 68% those failing metastases compared 35% in dacarbazine. Further IHC staining specimens taken from samples increased staining. We suggest may limit associated therapy.