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Targeting mTOR pathway inhibits tumor growth in different molecular subtypes of triple-negative breast cancers

Rana Hatem1,2, Rania El Botty3, Sophie Chateau-Joubert4

  • 1Genetics Department, Institut Curie, PSL Research University, Paris, France.

Oncotarget
|July 5, 2016
PubMed

Insights

The mTOR inhibitor everolimus showed anti-tumor activity in some triple-negative breast cancer (TNBC) models. Response to everolimus was linked to increased P-AKT after treatment, not baseline PI3K pathway markers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) often shows alterations in the PI3K/AKT/mTOR pathway.
  • Loss of tumor suppressors PTEN and INPP4B is common in TNBC, while PIK3CA/AKT1 mutations are rare.

Purpose of the Study:

  • To analyze PI3K pathway activation in TNBC patient-derived xenografts (PDX).
  • To investigate the anti-tumor efficacy of the mTOR inhibitor everolimus in TNBC PDX.
  • To identify predictive markers for everolimus response.

Main Methods:

  • Analysis of PI3K pathway markers in 67 TNBC PDX.
  • Treatment of 15 TNBC PDX models with everolimus.
  • Assessment of tumor growth inhibition and molecular markers post-treatment.

Main Results:

  • Everolimus inhibited tumor growth by over 50% in 7 out of 15 TNBC PDX models.
  • Response to everolimus was observed across various TNBC subtypes.
  • Increased post-treatment AKT phosphorylation (P-AKT) correlated with tumor response.

Conclusions:

  • mTOR inhibition with everolimus demonstrates anti-tumor effects in a subset of TNBC.
  • Tumor response to everolimus is not subtype-specific.
  • Post-treatment P-AKT levels are a potential biomarker for everolimus efficacy in TNBC.
Keywords:
PDXPI3K pathwayTNBCmTOR

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