title: Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway.
abstract: 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.
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Massihnia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galvano
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Fanale
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Perez
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Castiglia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Incorvaia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Listì
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cicero
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: Fondazione Mediterranea "G.B. Morgagni", Catania, Italy.|Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Castorina
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D005260:Female; D006801:Humans; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D058570:TOR Serine-Threonine Kinases
keywords: ER; HER2; PI3K/AKT/mTOR inhibitor; target therapy; triple negative breast cancer