Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway.
Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway.
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DOI：
10.18632/oncotarget.10858
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发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Russo A
中科院分区：
文献类型：
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作者：
Massihnia D;Galvano A;Fanale D;Perez A;Castiglia M;Incorvaia L;Listì A;Rizzo S;Cicero G;Bazan V;Castorina S;Russo A
乳腺癌是最常见的癌症之一，也是全世界癌症相关死亡的主要原因之一，尤其是 35 至 75 岁的女性。在不同的亚型中，三阴性乳腺癌 (TNBC) 的特点是完全不存在雌激素受体 (ER) 和孕激素受体 (PR) 表达，以及缺乏人表皮生长因子受体 2 (HER2) 过表达或基因扩增。与其他亚型相比，这些生物学特征使 TNBC 具有更高的侵袭性和复发风险，以及较差的预后。事实上，尽管有目前代表主流药理学方法的辅助治疗，但 5 年生存率仍然很低，几乎所有患者都会死亡。迄今为止，已经设计了多项临床试验来研究一些分子标记物（例如 VEGF、EGFR、Src 和 mTOR）在 TNBC 靶向治疗中的潜在作用。事实上，许多 PI3K/AKT/mTOR 通路抑制剂在 TNBC 中经常不受管制，正引起越来越多的兴趣，并且有几种抑制剂正处于临床前开发或已处于早期临床试验阶段。在这篇综述中，我们通过总结导致 TNBC 不同组织型区分的分子特征，研究了 PI3K/AKT/mTOR 通路在 TNBC 患者中的作用。此外，我们概述了 mTOR 和 PI3K/AKT 信号通路的抑制机制，强调了整合生物学和临床数据对于 mTOR 抑制剂开发的重要性，以便对 TNBC 患者实施靶向治疗。
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.