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Updated: Feb 16, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
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Functional characterization of a novel somatic oncogenic mutation of PIK3CB

Andrew D Whale1, Lucy Colman1, Letitia Lensun1

  • 1Karus Therapeutics Ltd., Genesis Building, Library Avenue, Harwell Campus, Oxfordshire, UK.

Signal Transduction and Targeted Therapy
|December 28, 2017
PubMed

Insights

Class I phosphoinositide 3-kinase (PI3K) enzymes are key in cancer. A PI3KCB mutation, p110βE1051K, drives tumor growth and migration, showing sensitivity to PI3K inhibition for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Class I phosphoinositide 3-kinase (PI3K) enzymes are crucial in cancer signaling pathways.
  • PI3K pathway dysregulation affects cell proliferation, survival, and apoptosis in various tumors.
  • While PIK3CA mutations are common, PIK3CB mutations are less reported but often oncogenic.

Purpose of the Study:

  • To functionally characterize the PIK3CB catalytic domain mutant, p110βE1051K.
  • To determine if p110βE1051K acts as a gain-of-function mutation driving cancer progression.
  • To assess the therapeutic potential of targeting p110β in tumors harboring this mutation.

Main Methods:

  • Functional characterization of the p110βE1051K mutant.
  • Assessment of PI3K signaling, cell growth, and migration in tumor cells expressing the mutant.
  • Evaluation of tumor cell sensitivity to p110β inhibition.

Main Results:

  • The p110βE1051K mutant demonstrates gain-of-function activity.
  • This mutation drives PI3K signaling, promoting tumorigenic cell growth and migration.
  • Tumor cells expressing p110βE1051K are sensitive to p110β inhibition.

Conclusions:

  • The p110βE1051K mutation is an oncogenic driver in cancer.
  • Targeting p110β is a viable therapeutic strategy for cancers with this mutation.
  • Further development of specific PI3K inhibitors is warranted for clinical application.

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