mRNA splicing variants: Exploiting modularity to outwit cancer therapy

  • Dehm S
  • 40

    Readers

    Mendeley users who have this article in their library.
  • 25

    Citations

    Citations of this article.

Abstract

Systemic cancer therapy has traditionally exploited vulnerabilities in cancer cells, a strategy which has become more precise with the identification and targeting of driver oncogenes. However, persistent tumor growth due to primary (de novo) or secondary (acquired) resistance limits therapeutic efficacy for many patients. Alternative splicing is important for increasing the diversity of the cellular proteome, and is a process frequently deregulated during cancer development and progression. In cancer cells, diverse splicing alterations have been identified that eliminate protein domains or enzymatic activities required for efficacy of cancer therapies, promote gain of novel signaling functions that circumvent cancer therapies, and uncouple signaling pathways from upstream regulatory points that are blocked by cancer therapies. The mechanisms underlying these splicing changes range from stable alterations in gene sequence/structure to deregulation of splicing regulatory factors. In this review, the role of splice variants in cancer therapy resistance will be discussed, with examples of how mechanistic understanding of these processes has led to the development of novel strategies for therapy resensitization.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Scott M. Dehm

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free