Effect of targeted degradation of androgen receptor full-length and variant-7 on gene expression in castration-resistant prostate cancer cells
The androgen receptor demonstrates transcriptional activity and, through the induction of related genes, contributes to the proliferation of prostate cancer cells. Despite the development of anti-prostate cancer therapies, resistance to current treatments persists in some patients. The expression of mutants or variants of androgen receptors is a significant factor in the emergence of resistance. Consequently, the targeted degradation of these mutants or variants of androgen receptors paves the way for the development of novel therapeutics for patients with castration-resistant prostate cancer. Our data provides the potential of the our novel TPD platform to target previously considered “undruggable” proteins and overcome certain drug resistance mechanisms Overall design: To investigate alterations in gene expression levels, we treated 22Rv1, an androgen-independent prostate cancer cell line, with a novel androgen receptor-targeting degrader. For the comparison of mRNA expression levels, we included control groups of 22Rv1 treated with the vehicle, enzalutamide, and an autophagy-activating ligand. Cells were treated with the indicated compounds for 24 hours and lysed with Trizol. We conducted gene expression profiling analysis using data from RNA-sequencing, with each group consisting of biologically independent triplicates.