Published online Oct 10, 2015. doi: 10.5306/wjco.v6.i5.92
Peer-review started: May 29, 2015
First decision: June 18, 2015
Revised: July 8, 2015
Accepted: July 29, 2015
Article in press: August 3, 2015
Published online: October 10, 2015
Processing time: 139 Days and 15.3 Hours
Alternative splicing (AS), the process of removing introns from pre-mRNA and re-arrangement of exons to give several types of mature transcripts, has been described more than 40 years ago. However, until recently, it has not been clear how extensive it is. Genome-wide studies have now conclusively shown that more than 90% of genes are alternatively spliced in humans. This makes AS one of the main drivers of proteomic diversity and, consequently, determinant of cellular function repertoire. Unsurprisingly, given its extent, numerous splice isoforms have been described to be associated with several diseases including cancer. Many of them have antagonistic functions, e.g., pro- and anti-angiogenic or pro- and anti-apoptotic. Additionally several splice factors have been recently described to have oncogene or tumour suppressors activities, like SF3B1 which is frequently mutated in myelodysplastic syndromes. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer. Approaches involving the use of oligonucleotides as well as small molecule splicing modulators are presented as well as thoughts on how specificity might be accomplished in splicing therapeutics.
Core tip: Genome-wide studies have recently shown that more than 90% of genes are alternatively spliced in humans. This makes alternative splicing (AS) one of the main drivers of proteomic diversity. Numerous splice isoforms have been described to be associated with cancer. Additionally several splice factors have been shown to have oncogene or tumour suppressors activities. Beside the implications for cancer pathogenesis, de-regulated AS is recognized as one of the novel areas of cell biology where therapeutic manipulations may be designed. This editorial discusses the possibilities of manipulation of AS for therapeutic benefit in cancer.