E-viri
Recenzirano
Odprti dostop
-
Hernandez‐Aya, Leonel F.; Gonzalez‐Angulo, Ana M.
The oncologist (Dayton, Ohio), 01/2011, Letnik: 16, Številka: 4Journal Article
Learning Objectives After completing this course, the reader will be able to: Describe how PTEN loss, PIK3CA mutations, and AKT dysregulation affect the phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling network in human breast cancer. Review the current state of AKT and mTOR inhibitor development, and describe its potential for clinical applications. This article is available for continuing medical education credit at CME.TheOncologist.com The phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) network plays a key regulatory function in cell survival, proliferation, migration, metabolism, angiogenesis, and apoptosis. Genetic aberrations found at different levels, either with activation of oncogenes or inactivation of tumor suppressors, make this pathway one of the most commonly disrupted in human breast cancer. The PI3K‐dependent phosphorylation and activation of the serine/threonine kinase AKT is a key activator of cell survival mechanisms. The activation of the oncogene PIK3CA and the loss of regulators of AKT including the tumor suppressor gene PTEN are mutations commonly found in breast tumors. AKT relieves the negative regulation of mTOR to activate protein synthesis and cell proliferation through S6K and 4EBP1. The common activation of the PI3K pathway in breast cancer has led to the development of compounds targeting the effector mechanisms of the pathway including selective and pan‐PI3K/pan‐AKT inhibitors, rapamycin analogs for mTOR inhibition, and TOR‐catalytic subunit inhibitors. The influences of other oncogenic pathways such as Ras‐Raf‐Mek on the PI3K pathway and the known feedback mechanisms of activation have prompted the use of compounds with broader effect at multiple levels and rational combination strategies to obtain a more potent antitumor activity and possibly a meaningful clinical effect. Here, we review the biology of the network, its role in the development and progression of breast cancer, and the evaluation of targeted therapies in clinical trials. 摘要 在细胞的存活、增殖、迁移、代谢、血管生成以及凋亡中,磷脂酰肌醇3激酶(PI3K)/AKT/哺乳类雷帕霉素靶蛋白(mTOR)信号网络起着关键的调节功能。该网络各个基因水平出现的遗传紊乱(无论是原癌基因激活还是抑癌基因失活所致)使其成为人类乳腺癌中最常见的异常之一。PI3K激活丝氨酸/苏氨酸激酶AKT依赖性的磷酸化是细胞存活的关键因素。癌基因PIK3CA激活和包括抑癌基因PTEN在内的AKT调节因子活性缺失是乳腺癌中最为常见的突变形式。AKT通过激活S6K和4EBP1,解除mTOR通路的负调控,促进蛋白合成及细胞增殖。乳腺癌中PI3K通路经常处于激活状态,因此可针对该通路的效应子机制开发化合物,包括pan‐PI3K/pan‐AKT选择性抑制剂、抑制mTOR的雷帕霉素类似物和催化TOR的亚基抑制剂。其他癌症发生通路(例如Ras‐Raf‐Mek对PI3K通路)的影响以及已知的活化反馈机制,在多个层面促使具有广泛效应的化疗物用于临床、合理的联合用药策略,以期获得更强效的抗癌活性以及可能的有意义的临床疗效。本文综述了该信号网络的生物学特征、其在乳腺癌发生发展中的作用,以及其在临床试验中靶向治疗的疗效评估。 The phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) network plays a key regulatory function in cell survival, proliferation, migration, metabolism, angiogenesis, and apoptosis. Genetic aberrations found at different levels make this pathway one of the most commonly disrupted in human breast cancer. Because the PI3K pathway has divergent downstream effects, the identification of the key effectors of the pathway and their presence in the different subtypes of breast tumors will allow the development of ideal targeted therapies with meaningful clinical efficacy.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.