Current Breast Cancer Reports

, Volume 6, Issue 2, pp 59–70 | Cite as

The PI3K/AKT/MTOR Signaling Pathway: The Role of PI3K and AKT Inhibitors in Breast Cancer

Systemic Therapy (J Cortes, Section Editor)

Abstract

Breast cancer is the second leading cause of cancer death in women. Targeted therapies are available for HER2-positive and endocrine-sensitive disease while chemotherapy remains the mainstay of treatment for triple-negative breast cancer. The efficacy of all targeted interventions is, however, limited by primary or secondary resistance. Preclinical data show that active PI3K/AKT/mTOR signaling contributes to therapy resistance in HER2-positive and hormone-receptor-positive breast cancer. In line with these preclinical observations, clinical trials such as BOLERO-2 demonstrated a benefit of additional inhibition of mTOR signaling in advanced estrogen-receptor-positive breast cancer patients refractory to prior aromatase-inhibitor therapy. Besides the mTOR, several other proteins involved in the PI3K-pathway serve as potential therapeutic targets, such as PI3K and AKT. In this review, we summarize the current available knowledge and experimental and clinical research results about targeting the PI3K-pathway in breast cancer and, thus, provide the rationale for PI3K- and AKT-inhibitor use in the clinic.

Keywords

Cancer Breast PI3K MAPK p110 AKT mTOR mTORC1 mTORC2 Rictor Raptor PIK3CA PTEN Resistance Feedback Crosstalk XL147 BKM120 BYL719 BEZ235 INK1117 MK-2206 Rapalogue Everolimus Temsirolimus 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Florian Huemer
    • 1
    • 2
  • Rupert Bartsch
    • 1
    • 2
  • Michael Gnant
    • 1
    • 3
  1. 1.Comprehensive Cancer Center ViennaMedical University of ViennaViennaAustria
  2. 2.Department of Medicine IMedical University of ViennaViennaAustria
  3. 3.Department of Surgery and Comprehensive Cancer CenterMedical University of ViennaViennaAustria

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