Androgen receptor is a determinant of melanoma targeted drug resistance.

ABSTRACT: Melanoma provides a primary benchmark for targeted drug therapy. Most melanomas with BRAF^V600 mutations regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). However, nearly all relapse within the first two years, and there is a connection between BRAFi/MEKi-resistance and poor response to immune checkpoint therapy. We reported that androgen receptor (AR) activity is required for melanoma cell proliferation and tumorigenesis. We show here that AR expression is markedly increased in BRAFi-resistant melanoma cells, and in sensitive cells soon after BRAFi exposure. Increased AR expression is sufficient to render melanoma cells BRAFi-resistant, eliciting transcriptional changes of BRAFi-resistant subpopulations, including elevated EGFR and SERPINE1 expression, of likely clinical

SUBMITTER: Samarkina A 

PROVIDER: S-EPMC10576812 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature