Targeting alternative splicing in prostate oncology

Abstract

Prostate cancer is the most common cancer seen in aging males in the Western world, and is a major clinical challenge in uro-oncology due to biological heterogeneity. Recent advances in molecular medicine suggest that the genetic composition of a prostate tumor contributes significantly to the complexity of the disease. An important genetic mechanism underlying biological diversity is alternative pre-mRNA splicing, which is thought to affect approximately 95% of transcripts derived from protein-encoding genes. During alternative splicing, coding (exons) and non-coding (introns) regions of pre-messenger RNA (pre-mRNA) transcripts derived from a single gene are rearranged to generate several mRNAs species, which are translated into distinct protein isoforms with differing biological functions. Recent emerging evidence suggests that prostate cancer-specific aberrant and alternative splicing may contribute to the biological heterogeneity of the disease. Furthermore, identification of prostate cancer-specific splice variants may yield novel biomarkers and targets for therapy to improve patient care and clinical outcome.