Therapeutic targeting of splicing in cancer Review uri icon

Overview

MeSH Major

  • Alternative Splicing
  • Gene Expression Regulation, Neoplastic
  • Neoplasms
  • RNA Splicing
  • RNA Splicing Factors
  • Spliceosomes

abstract

  • Recent studies have highlighted that splicing patterns are frequently altered in cancer and that mutations in genes encoding spliceosomal proteins, as well as mutations affecting the splicing of key cancer-associated genes, are enriched in cancer. In parallel, there is also accumulating evidence that several molecular subtypes of cancer are highly dependent on splicing function for cell survival. These findings have resulted in a growing interest in targeting splicing catalysis, splicing regulatory proteins, and/or specific key altered splicing events in the treatment of cancer. Here we present strategies that exist and that are in development to target altered dependency on the spliceosome, as well as aberrant splicing, in cancer. These include drugs to target global splicing in cancer subtypes that are preferentially dependent on wild-type splicing for survival, methods to alter post-translational modifications of splicing-regulating proteins, and strategies to modulate pathologic splicing events and protein-RNA interactions in cancer.

publication date

  • September 7, 2016

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC5644489

Digital Object Identifier (DOI)

  • 10.1038/nm.4165

PubMed ID

  • 27603132

Additional Document Info

start page

  • 976

end page

  • 86

volume

  • 22

number

  • 9