Current Breast Cancer Reports

, Volume 6, Issue 2, pp 59–70

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

Systemic Therapy (J Cortes, Section Editor)

DOI: 10.1007/s12609-014-0139-y

Cite this article as:
Huemer, F., Bartsch, R. & Gnant, M. Curr Breast Cancer Rep (2014) 6: 59. doi:10.1007/s12609-014-0139-y


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.



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