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

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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.
Lingua originaleEnglish
pagine (da-a)60712-60722
Numero di pagine11
RivistaOncotarget
Volume7
Stato di pubblicazionePublished - 2016

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Triple Negative Breast Neoplasms
Phosphatidylinositol 3-Kinases
Clinical Trials
erbB-1 Genes
Gene Amplification
Progesterone Receptors
Estrogen Receptors
Vascular Endothelial Growth Factor A
Therapeutics
Survival Rate
Pharmacology
Breast Neoplasms
Carcinoma
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology

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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.",
keywords = "ER, HER2, Oncology, PI3K/AKT/mTOR inhibitor, Target therapy, Triple negative breast cancer",
author = "Daniele Fanale and Daniela Massihnia and Angela Listi' and Marta Castiglia and Alessandro Perez and Antonio Russo and Lorena Incorvaia and Antonio Galvano and Viviana Bazan and Giuseppe Cicero and Sergio Castorina and Sergio Rizzo",
year = "2016",
language = "English",
volume = "7",
pages = "60712--60722",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",

}

TY - JOUR

T1 - Triple negative breast cancer: Shedding light onto the role of pi3k/akt/mtor pathway

AU - Fanale, Daniele

AU - Massihnia, Daniela

AU - Listi', Angela

AU - Castiglia, Marta

AU - Perez, Alessandro

AU - Russo, Antonio

AU - Incorvaia, Lorena

AU - Galvano, Antonio

AU - Bazan, Viviana

AU - Cicero, Giuseppe

AU - Castorina, Sergio

AU - Rizzo, Sergio

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - ER

KW - HER2

KW - Oncology

KW - PI3K/AKT/mTOR inhibitor

KW - Target therapy

KW - Triple negative breast cancer

UR - http://hdl.handle.net/10447/192235

UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=10858&path%5B%5D=34372

M3 - Article

VL - 7

SP - 60712

EP - 60722

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

ER -