Splicing targeting approaches highlight actionable vulnerabilities in advanced prostate cancer [22Rv1]

To investigate if pharmacological inhibition of splicing could uncover novel actionable vulnerabilities in CRPC, we profiled the genome-wide transcriptional changes elicited in 22Rv1 cells by treatment with three drugs that inhibit the splicing through different molecular targets: i. Pladienolide B, that impairs the activity of SF3B1; ii. Indisulam that promote degradation of the splicing factor RBM39; iii. THZ531 inhibits the cyclin dependent kinases (CDK) 12 and 13. Poly-A plus RNA-sequencing of 22Rv1 cells treated with Indisulam (3.3µM, 12hrs), or Pladienolide B (10nM, 6hrs) or THZ531 (200nM, 6hrs) or DMSO as control.