Related Experiment Video

Updated: Oct 13, 2025

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
08:59

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma

Published on: January 5, 2017

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Therapeutic implications of activating noncanonical PIK3CA mutations in head and neck squamous cell carcinoma

Nan Jin1, Bhumsuk Keam2, Janice Cho1

  • 1Department of Otolaryngology, Head and Neck Surgery, University of California San Francisco, San Francisco, California, USA.

The Journal of Clinical Investigation
|November 15, 2021
PubMed

Insights

Alpelisib shows promise for head and neck cancers with noncanonical PIK3CA mutations. This study found many noncanonical mutations are activating, suggesting PI3Kα inhibitors may benefit these patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alpelisib targets PI3Kα, approved for PIK3CA-mutated breast cancers.
  • Head and neck squamous cell carcinoma (HNSCC) has frequent PIK3CA mutations, with 37% being noncanonical and poorly understood.
  • Canonical PIK3CA mutations are common in HNSCC (63%).

Purpose of the Study:

  • To investigate the oncogenic role of noncanonical PIK3CA mutations in HNSCC.
  • To evaluate the efficacy of alpelisib in HNSCC patients with noncanonical PIK3CA mutations.
  • To characterize the functional impact of noncanonical PIK3CA mutations.

Main Methods:

  • Phase II clinical trial of alpelisib in HNSCC patients.
  • Functional and phenotypic assays to characterize 32 noncanonical PIK3CA mutations.
  • Cellular models and xenograft studies to validate oncogenic impact and drug efficacy.
  • Structural analyses to elucidate mutation mechanisms.

Main Results:

  • A patient with HNSCC and a noncanonical PIK3CA mutation (Q75E) experienced a durable 12-month response to alpelisib.
  • 69% of characterized noncanonical PIK3CA mutations in HNSCC were activating, including Q75E.
  • Alpelisib demonstrated antitumor effects in an HNSCC xenograft with an activating noncanonical PIK3CA mutation.

Conclusions:

  • Activating noncanonical PIK3CA mutations are common in HNSCC and contribute to oncogenesis.
  • Alpelisib may be a viable treatment option for HNSCC patients with activating noncanonical PIK3CA mutations.
  • Further characterization of noncanonical PIK3CA mutations is crucial for personalized cancer therapy.
Keywords:
Head and neck cancerOncology

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