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Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer

Fatemeh Mazloumi Gavgani1, Victoria Smith Arnesen2, Rhîan G Jacobsen3

  • 1Department of Biological Science, University of Bergen, 5008 Bergen, Norway. Fatemeh.Mazloumi.Gavgani@uib.no.

International Journal of Molecular Sciences
|December 15, 2018
PubMed

Insights

The phosphoinositide 3-kinase (PI3K) pathway is frequently altered in endometrial cancer, particularly involving PIK3CA and PTEN. This review explores PI3K isoforms p110α and p110β, their roles, and clinical targeting.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The phosphoinositide 3-kinase (PI3K) signaling pathway is crucial for cellular processes and frequently dysregulated in cancer.
  • Endometrial carcinomas exhibit common alterations in PI3K pathway components, including PIK3CA (encoding p110α) and PTEN.
  • While PIK3CB (encoding p110β) is less frequently mutated, its oncogenic potential is recognized, especially in PTEN-deficient tumors.

Purpose of the Study:

  • To review the current understanding of the biochemical properties of PI3K isoforms p110α and p110β.
  • To summarize mutations affecting these isoforms in endometrial cancer.
  • To highlight therapeutic strategies targeting these PI3K isoforms in clinical trials for endometrial cancer.

Main Methods:

  • Literature review of PI3K pathway dysregulation in endometrial cancer.
  • Analysis of common and distinct biochemical properties of p110α and p110β isoforms.
  • Summary of mutation data and clinical trial information for PI3K-targeted therapies.

Main Results:

  • PIK3CA mutations are frequent in endometrial cancer, driving oncogenic signaling.
  • PTEN loss is common and can lead to dependency on p110β activity.
  • Both p110α and p110β isoforms are implicated in endometrial tumorigenesis.

Conclusions:

  • Understanding the distinct roles and mutations of p110α and p110β is critical for endometrial cancer treatment.
  • Targeting PI3K isoforms p110α and p110β offers promising therapeutic avenues.
  • Ongoing clinical trials are evaluating the efficacy of PI3K-targeted agents in endometrial cancer.
Keywords:
PIK3CAPIK3CBendometrial cancerp110αp110βphosphoinositide 3-kinase

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