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

  • Systemic Therapy (J Cortes, Section Editor)
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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.

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Conflict of Interest

In the last three years, Michael Gnant has received institutional research support from Sanofi-aventis, Novartis, Roche, Pfizer. He also discloses honoraria (speaking, advisory boards, etc.) and travel support from Amgen, Novartis, GlaxoSmithKline, AstraZeneca, Nanostring Technologies.

Rupert Bartsch has received lecture honoraria, research and travel support from Novartis Austria.

Florian Huemer declares that he does not have any conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria

    Florian Huemer, Rupert Bartsch & Michael Gnant

  2. Department of Medicine I, Medical University of Vienna, Vienna, Austria

    Florian Huemer & Rupert Bartsch

  3. Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, A-1090, Vienna, Waehringer Guertel 18-20, Austria

    Michael Gnant

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  1. Florian Huemer
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Correspondence to Michael Gnant.

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Huemer, F., Bartsch, R. & Gnant, M. The PI3K/AKT/MTOR Signaling Pathway: The Role of PI3K and AKT Inhibitors in Breast Cancer. Curr Breast Cancer Rep 6, 59–70 (2014). https://doi.org/10.1007/s12609-014-0139-y

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