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The Strategy of PIKing a Target: What Is AKTually Most Effective?

Carlotta Costa1, Ana Bosch2

  • 1Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts. ana.bosch_campos@med.lu.se carlotta.costa@novartis.com.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 28, 2018
PubMed

Insights

AZD5363, a pan-AKT inhibitor, did not show significant response in breast and gynecologic cancers with PIK3CA mutations, contrary to in vitro findings. This highlights the need for better predictive biomarkers to guide treatment selection.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • PIK3CA mutations are common in breast and gynecologic cancers.
  • AKT signaling pathway is a target for cancer therapy.
  • AZD5363 is a potent inhibitor of AKT.

Purpose of the Study:

  • To evaluate the efficacy of AZD5363 in patients with PIK3CA-mutated breast and gynecologic cancers.
  • To assess the predictive value of PIK3CA mutations for response to AZD5363.
  • To identify potential biomarkers for patient selection in clinical trials.

Main Methods:

  • Phase I/II clinical trial.
  • Patients with advanced breast and gynecologic cancers harboring PIK3CA mutations were enrolled.
  • Tumor response was assessed using RECIST criteria.
  • Pharmacokinetic and pharmacodynamic analyses were performed.

Main Results:

  • No significant objective responses were observed in patients treated with AZD5363.
  • The drug was generally well-tolerated.
  • In vitro studies previously suggested sensitivity of PIK3CA-mutated cancers to AZD5363.
  • Clinical efficacy did not correlate with in vitro findings.

Conclusions:

  • AZD5363 is not an effective treatment for PIK3CA-mutated breast and gynecologic cancers.
  • PIK3CA mutation status alone is not a sufficient predictive biomarker for AZD5363 response.
  • Further research is needed to identify reliable predictive biomarkers for AKT inhibitors.

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