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PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors

Filip Janku1, Apostolia M Tsimberidou, Ignacio Garrido-Laguna

  • 1Department of Investigational Cancer Therapeutics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., FC8.2057, Box 0455, Houston, TX 77030, USA.

Molecular Cancer Therapeutics
|January 11, 2011
PubMed

Insights

PIK3CA mutations in diverse solid tumors predict a better response to PI3K/AKT/mTOR inhibitors. However, concurrent KRAS or BRAF mutations may indicate resistance, particularly in colorectal cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Preclinical studies indicate PIK3CA mutations are predictive of response to PI3K/AKT/mTOR inhibitors.
  • Concomitant KRAS or BRAF mutations might confer resistance to these targeted therapies.

Purpose of the Study:

  • To analyze PIK3CA mutations in patients with diverse solid tumors referred for targeted therapy.
  • To evaluate the efficacy of PI3K/AKT/mTOR pathway inhibitors in patients with and without PIK3CA mutations.

Main Methods:

  • PCR-based DNA sequencing of PIK3CA exons 9 and 20 was performed on tumors from patients in a phase I program.
  • Patients with PIK3CA mutations were treated with PI3K/AKT/mTOR pathway inhibitors when feasible.
  • Response rates were compared between patients with and without PIK3CA mutations.

Main Results:

  • PIK3CA mutations were identified in 11.5% (25/217) of patients across various solid tumors.
  • Higher response rates (35%) were observed in PIK3CA-mutated patients treated with PI3K/AKT/mTOR inhibitors compared to those without mutations (6%).
  • Simultaneous KRAS or BRAF mutations were present in 35% (6/17) of PIK3CA-mutated patients, impacting treatment response differently across tumor types.

Conclusions:

  • PIK3CA mutations are present in a significant subset of patients with diverse solid tumors.
  • Targeted therapy against the PI3K/AKT/mTOR pathway shows higher efficacy in PIK3CA-mutated patients.
  • The presence of concurrent KRAS or BRAF mutations warrants further investigation for predicting resistance to PI3K/AKT/mTOR inhibitors.

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