Splicing targeting drugs highlight intron retention as an actionable vulnerability in advanced prostate cancer.

ABSTRACT:

Background

Advanced prostate cancer (PC) is characterized by insensitivity to androgen deprivation therapy and chemotherapy, resulting in poor outcome for most patients. Thus, advanced PC urgently needs novel therapeutic strategies. Mounting evidence points to splicing dysregulation as a hallmark of advanced PC. Moreover, pharmacologic inhibition of the splicing process is emerging as a promising option for this disease.

Method

By using a representative androgen-insensitive PC cell line (22Rv1), we have investigated the genome-wide transcriptomic effects underlying the cytotoxic effects exerted by three splicing-targeting drugs: Pladienolide B, indisulam and THZ531. Bioinformatic analyses were performed to uncover the gene structural features underlying sensitivity to transc

SUBMITTER: Naro C 

PROVIDER: S-EPMC10898177 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature