Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

Daniela Massihnia, Antonio Galvano, Daniele Fanale, Alessandro Perez, Marta Castiglia, Lorena Incorvaia, Angela Listì, Sergio Rizzo, Giuseppe Cicero, Viviana Bazan, Sergio Castorina and Antonio Russo _

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Oncotarget. 2016; 7:60712-60722. https://doi.org/10.18632/oncotarget.10858

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Daniela Massihnia1,*, Antonio Galvano1,*, Daniele Fanale1, Alessandro Perez1, Marta Castiglia1, Lorena Incorvaia1, Angela Listì1, Sergio Rizzo1, Giuseppe Cicero1, Viviana Bazan1, Sergio Castorina2,3,** and Antonio Russo1,**

1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy

2 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy

3 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

* These authors have contributed equally to this work

** Both the authors are last name

Correspondence to:

Antonio Russo, email:

Keywords: ER, HER2, PI3K/AKT/mTOR inhibitor, target therapy, triple negative breast cancer

Received: April 28, 2016 Accepted: July 14, 2016 Published: July 26, 2016


Breast cancer is one of the most widespread carcinoma and one of the main causes of cancer-related death worldwide, especially in women aged between 35 and 75 years. Among the different subtypes, triple negative breast cancer (TNBC) is characterized by the total absence of the estrogen-receptor (ER) and progesteron-receptor (PR) expression as well as the lack of human epidermal growth factor receptor 2 (HER2) overexpression or gene amplification. These biological characteristics confer to TNBC a higher aggressiveness and relapse risk along with poorer prognosis compared to other subtypes. Indeed, 5-years survival rate is still low and almost all patients die, despite any adjuvant treatment which at moment represents the heading pharmacological approach. To date, several clinical trials have been designed to investigate the potential role of some molecular markers, such as VEGF, EGFR, Src and mTOR, for targeted treatments in TNBC. In fact, many inhibitors of the PI3K/AKT/mTOR pathway, frequently de-regulated in TNBC, are acquiring a growing interest and several inhibitors are in preclinical development or already in early phase clinical trials. In this Review, we investigated the role of the PI3K/AKT/mTOR pathway in TNBC patients, by summarizing the molecular features that led to the distinction of different histotypes of TNBC. Furthermore, we provided an overview of the inhibition mechanisms of the mTOR and PI3K/AKT signaling pathways, highlighting the importance of integrating biological and clinical data for the development of mTOR inhibitors in order to implement targeted therapies for TNBC patients.

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