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PIK3CA-related overgrowth: silver bullets from the cancer arsenal?

Ralitsa R Madsen1, Robert K Semple2

  • 1University College London (UCL) Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E 6DD, UK.

Trends in Molecular Medicine
|March 11, 2022
PubMed

Insights

Mutations in PIK3CA can cause both cancer and developmental disorders. This review discusses progress in repurposing cancer drugs to treat PIK3CA-driven overgrowth conditions.

Area of Science:

  • Oncology
  • Genetics
  • Developmental Biology

Background:

  • Growth factor signaling pathways are crucial for normal development and cell growth.
  • Aberrant activation of these pathways, particularly involving PIK3CA, is implicated in various cancers and developmental disorders.
  • PIK3CA encodes a key enzyme in the phosphatidylinositol 3-kinase (PI3K) pathway, a central regulator of cell proliferation, survival, and metabolism.

Purpose of the Study:

  • To review recent advancements in understanding PIK3CA-driven overgrowth.
  • To explore the potential of repurposing existing cancer drugs for treating PIK3CA-related disorders.
  • To highlight the therapeutic strategies for conditions caused by PIK3CA mutations.

Main Methods:

  • Literature review of recent research on PIK3CA mutations and their effects.
  • Analysis of drug repurposing strategies for PIK3CA-driven conditions.
  • Synthesis of findings on therapeutic interventions.

Main Results:

  • PIK3CA mutations are a common driver in both oncogenesis and developmental overgrowth syndromes.
  • Targeting the PI3K/AKT pathway is a promising therapeutic strategy.
  • Drug repurposing offers a viable approach to accelerate treatment development for these conditions.

Conclusions:

  • PIK3CA mutations represent a significant target for therapeutic intervention in both cancer and developmental disorders.
  • Repurposing drugs initially developed for cancer treatment holds great promise for managing PIK3CA-driven overgrowth.
  • Further research is needed to optimize drug efficacy and minimize side effects for these specific patient populations.
Keywords:
CLOVESPI3KPIK3CAPROSalpelisibovergrowthphosphatidylinositol 3-kinasesirolimustrials

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