Antibody Dependent Cellular Cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors

ABSTRACT: The efficacy of BRAF inhibitors (BRAFi) in cutaneous melanoma (CM) is impaired by resistance mechanisms, often accompanied by receptor tyrosine kinases (RTKs) up-regulation. We investigated whether up-regulated RTKs could be exploited as targets for the immune-mediated effects of anti-RTKs antibodies. Increased membrane expression of EGFR, and up-regulated levels of its ligand NRG1, were detected in 4 out of 9 BRAFi-resistant (VR) CM cultures as compared to their parental sensitive cells. RTKs expression was confirmed in CM tissues. Increased EGFR phosphorylation and AKT activation were observed. EGFR signaling appeared dispensable for maintaining resistance, since small molecule-, antibody- and CRISPR-targeting of EGFR did not restore sensitivity of VR cells to BRAFi. Importantly, immune-

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST1225 | biostudies-other |

REPOSITORIES: biostudies-other