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Published on: July 17, 2020

Functional characterization of an isoform-selective inhibitor of PI3K-p110β as a potential anticancer agent

Jing Ni1, Qingsong Liu, Shaozhen Xie

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02115, USA.

Cancer Discovery
|May 17, 2012
PubMed
Abstract

Insights

Researchers identified KIN-193, a selective inhibitor targeting p110β (phosphatidylinositol-3-kinase beta). This drug effectively blocks tumor growth in PTEN-deficient cancers, offering a promising new cancer therapy strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Class Ia phosphatidylinositol-3-kinase (PI3K) p110β isoform is crucial for PTEN-null tumor growth.
  • Development of p110β-specific inhibitors is a key goal for cancer therapy.

Purpose of the Study:

  • To identify and characterize a selective p110β inhibitor for potential cancer treatment.
  • To evaluate the efficacy of p110β inhibition in PTEN-deficient tumors.

Main Methods:

  • Screening of PI3K superfamily kinase inhibitors using PI3K isoform-specific cellular assays.
  • Profiling KIN-193 across 422 human tumor cell lines to assess PTEN mutation status correlation.
  • Evaluating KIN-193's antitumor efficacy in mouse models.

Main Results:

  • KIN-193 identified as a potent and selective p110β inhibitor.
  • KIN-193 effectively blocks AKT signaling and tumor growth dependent on p110β or PTEN loss.
  • PTEN mutation status strongly correlates with tumor cell response to KIN-193.

Conclusions:

  • KIN-193 is the first functionally characterized p110β-selective inhibitor with demonstrated antitumor efficacy in mice.
  • p110β-selective inhibitors, like KIN-193, show significant promise for treating p110β-dependent PTEN-deficient human tumors.

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