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Synthetic lethal approaches to target cancers with loss of PTEN function

Ayse Ertay1, Rob M Ewing1,2, Yihua Wang1,2

  • 1Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.

Genes & Diseases
|August 3, 2023
PubMed

Insights

Inactive phosphatase and tensin homolog (PTEN) drives aggressive cancers. This review explores synthetic lethality, identifying potential targeted therapies for PTEN-inactive cancers to improve treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Phosphatase and tensin homolog (PTEN) is a crucial tumor suppressor gene.
  • PTEN normally inhibits the AKT signaling pathway by regulating phosphatidylinositol (PI) levels.
  • Loss or inactivation of PTEN function is linked to aggressive tumor phenotypes and tumorigenesis.

Purpose of the Study:

  • To review potential synthetic lethality gene targets in PTEN-inactive cancers.
  • To explore novel therapeutic strategies for cancers with deficient PTEN.
  • To identify targets that can improve treatment response in aggressive cancers.

Main Methods:

  • Literature review focusing on synthetic lethality studies.
  • Analysis of genes identified as synthetic lethal in PTEN-deficient cancer models.
  • Examination of downstream signaling pathways affected by PTEN inactivation.

Main Results:

  • Several genes have been identified as synthetically lethal in PTEN-inactive cancer contexts.
  • These genes represent potential targets for novel cancer therapies.
  • Targeting these synthetic lethal partners offers a promising strategy when direct PTEN restoration is not feasible.

Conclusions:

  • Synthetic lethality offers a viable therapeutic approach for PTEN-inactive cancers.
  • The identified genes hold potential as drug targets to treat aggressive cancers.
  • Further research into these targets may lead to improved patient outcomes and treatment efficacy.
Keywords:
CancerPTENSynthetic lethalityTumour suppressor geneWDHD1

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