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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Published on: April 26, 2017

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Roles and mechanisms of alternative splicing in cancer - implications for care

Sophie C Bonnal1,2, Irene López-Oreja1,2,3, Juan Valcárcel4,5,6

  • 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.

Nature Reviews. Clinical Oncology
|April 19, 2020
PubMed

Insights

Messenger RNA (mRNA) splicing alterations are common in cancer, impacting disease progression and immune response. Targeting these splicing defects with novel therapies offers promising personalized cancer treatment strategies.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • Pre-messenger RNA (pre-mRNA) splicing is crucial for eukaryotic gene expression.
  • Alternative splicing allows a single gene to produce multiple mRNA and protein variants.
  • Cancer cells exhibit altered splicing patterns, which can be prognostic and drive cancer hallmarks.

Purpose of the Study:

  • To review the role of splicing alterations in cancer.
  • To highlight the therapeutic potential of targeting splicing in cancer treatment.

Main Methods:

  • Review of scientific literature on pre-mRNA splicing, alternative splicing, and cancer biology.
  • Analysis of the link between splicing machinery mutations and cancer development.
  • Examination of current and emerging splicing-targeted cancer therapies.

Main Results:

  • Splicing alterations are prevalent in various cancers, correlating with driver mutations and contributing to cancer hallmarks.
  • Altered splicing impacts cancer immune responses.
  • Cancer cells' transcriptomic profile creates vulnerabilities exploitable by splicing inhibitors.

Conclusions:

  • Dysregulated splicing is a significant feature of cancer, offering prognostic insights.
  • Pharmacological inhibition of splicing, including small-molecule modulators and antisense oligonucleotides, represents a promising therapeutic avenue for personalized cancer treatment.

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