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Updated: Jan 13, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
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Early phase development of PI3kinase inhibitors for anticancer therapies

Carlo Caputo1,2, Angela Lombardi2,3, Margherita Vicario1

  • 1Laboratory of Molecular and Precision Oncology, Institute of Genetic Research, Biogem Scarl, Ariano Irpino, Italy.

Expert Opinion on Investigational Drugs
|October 28, 2025
PubMed
Abstract

Insights

The PI3K/Akt/mTOR pathway is vital for cell functions, but its abnormal activation fuels cancer. PI3KCA genetic alterations are common, making PI3KCA inhibitors a promising cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The PI3K/Akt/mTOR pathway regulates cell proliferation, survival, and metabolism.
  • Aberrant activation of this pathway drives tumor development and progression.
  • Genetic alterations in PI3KCA, encoding the p110α subunit, are frequent oncogenic features in various cancers.

Purpose of the Study:

  • To review current knowledge on the PI3K/Akt/mTOR pathway, focusing on PI3KCA genetic alterations in tumorigenesis.
  • To discuss the therapeutic potential of PI3KCA inhibitors in different cancer types.
  • To highlight the limitations and challenges associated with PI3KCA inhibitor therapy.

Main Methods:

  • Literature review of PI3K/Akt/mTOR pathway and PI3KCA genetic alterations.
  • Analysis of approved and investigational PI3KCA inhibitors.
  • Discussion of clinical outcomes, efficacy, and toxicity of PI3KCA inhibitors.

Main Results:

  • PI3KCA mutations/amplifications are prevalent in many cancers, identifying PI3KCA as a key therapeutic target.
  • PI3KCA inhibitors show promise as a targeted therapy for tumors with mutated p110α.
  • Current challenges include managing patient efficacy and toxicity.

Conclusions:

  • PI3KCA-specific inhibitors offer a novel therapeutic strategy for specific cancer types.
  • Optimizing treatment requires molecular patient stratification via genomic profiling.
  • Developing targeted combination therapies is crucial for maximizing benefits and improving patient outcomes.
Keywords:
CancerPI3K/Akt/mTOR pathwaycombinationinhibitormutationtargeted therapy

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