Targeting splicing in prostate cancer
International Journal of Molecular Sciences, accepted (2018) -
Authors: Effrosyni Antonopoulou, Michael Ladomery
Over 95% of human genes are alternatively spliced, expressing splice isoforms that often exhibit antagonistic functions. We describe genes whose alternative splicing has been linked to prostate cancer; namely VEGF-A, KLF6, BCL2L2, ERG, and AR. We discuss opportunities to develop novel therapies that target specific splice isoforms, or that target the machinery of splicing. Therapeutic approaches include the development of small molecule inhibitors of splice factor kinases, splice isoform specific siRNAs, and splice switching oligonucleotides.
Keywords: Alternative splicing; prostate cancer; VEGFA; KLF6; BCL2L2; ERG; AR; splice switching oligonucleotides; RNA interference; splice factors; splice factor kinases