GSE138751 Therapeutic targeting MDR1 expression by ROR γ antagonists resensitizes cross-resistant CRPC to taxane via coordinated induction of cell death programs

We report here that ROR γ, a nuclear receptor family member, unexpectedly mediates MDR1/ABCB1 overexpression. RORγ plays an important role in controlling the functions of subsets of immune cells and has been an attractive target for autoimmune diseases. We found that its small-molecule antagonists are efficacious in re-s ensitizing DTX and CTX cross-resistant CRPC cells and tumors to taxanes in both androgen receptor (AR)-positive and -negative models. Our mechanistic analyses revealed that combined treatment with RORγ antagonists and taxane elicited a robust synergy in killing the resistant cells, which involves a coordinated alteration of p53, Myc and E2F-controlled programs critical for both intrinsic and extrinsic apoptosis, survival and cell growth. Our results suggest that targeting RORγ with small-molecule inhibitors is a novel strategy for chemotherapy resensitization in tumors with MDR1 overexpressi on.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research