Sox10-Deficient Drug-Resistant Melanoma Cells Are Refractory to Oncolytic RNA Viruses.

ABSTRACT: Targeted therapy resistance frequently develops in melanoma due to intratumor heterogeneity and epigenetic reprogramming. This also typically induces cross-resistance to immunotherapies. Whether this includes additional modes of therapy has not been fully assessed. We show that co-treatments of MAPKi with VSV-based oncolytics do not function in a synergistic fashion; rather, the MAPKis block infection. Melanoma resistance to vemurafenib further perturbs the cells' ability to be infected by oncolytic viruses. Resistance to vemurafenib can be induced by the loss of SOX10, a common proliferative marker in melanoma. The loss of SOX10 promotes a cross-resistant state by further inhibiting viral infection and replication. Analysis of RNA-seq datasets revealed an upregulation of interferon-stimul

SUBMITTER: Abou-Hamad J 

PROVIDER: S-EPMC10777920 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature