Glucocorticoid receptor antagonism overcomes resistance to BRAF inhibition in BRAF^V600E-mutated metastatic melanoma.

ABSTRACT: Clinical applications of glucocorticoids (GC) in Oncology are dependent on their pro-apoptotic action to treat lymphoproliferative cancers, and to alleviate side effects induced by chemotherapy and/or radiotherapy. However, the mechanism(s) by which GC may also promote tumor progression remains unclear. GC receptor (GR) knockdown decreases the antioxidant protection of highly metastatic B16-F10 melanoma cells. We hypothesize that a GR antagonist (RU486, mifepristone) could increase the efficacy of BRAF-related therapy in BRAF^V600E-mutated metastatic melanoma. In vivo formed spontaneous skin tumors were reinoculated into nude mice to expand the metastases of different human BRAF^V600E melanoma cells. The GR content of melanoma cell lines was measured by [^3</

SUBMITTER: Estrela JM 

PROVIDER: S-EPMC6943348 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature