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程序性细胞死亡途径与当前的抗肿瘤靶点。

Programmed cell death pathways and current antitumor targets.

作者信息

Tan Mei Lan, Ooi Jer Ping, Ismail Nawfal, Moad Ahmed Ismail Hassan, Muhammad Tengku Sifzizul Tengku

机构信息

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Lot 1-8, Persiaran Seksyen 4/1, Bandar Putra Bertam, Kepala Batas, Pulau Pinang, Malaysia.

出版信息

Pharm Res. 2009 Jul;26(7):1547-60. doi: 10.1007/s11095-009-9895-1. Epub 2009 Apr 30.

Abstract

Apoptosis and autophagic cell deaths are programmed cell deaths and they play essential roles in cell survival, growth and development and tumorigenesis. The huge increase of publications in both apoptosis and autophagic signaling pathways has contributed to the wealth of knowledge in facilitating the understanding of cancer pathogenesis. Deciphering the molecular pathways and molecules involved in these pathways has helped scientists devise and develop targeted strategies against cancer. Various drugs targeting the apoptotic TRAIL, Bcl-2 and proteasome pathways are already in Phase II/III clinical trials. The first mTOR inhibitor, temsirolimus has already been approved by the FDA, USA for the treatment of advanced renal cell carcinoma and more mTOR inhibitors are expected to be in the market in a few years time. Strategizing against aberrant autophagy activities in various cancers by using either pro-autophagics or autophagy inhibitors are currently been investigated. This review aims to discuss the most recent antitumor strategies targeting the apoptosis and autophagy signaling pathways and the latest outcome of clinical trials of the above drugs.

摘要

凋亡和自噬性细胞死亡是程序性细胞死亡,它们在细胞存活、生长、发育以及肿瘤发生过程中发挥着重要作用。凋亡和自噬信号通路相关出版物数量的大幅增加,为促进对癌症发病机制的理解积累了丰富的知识。解析这些通路中涉及的分子途径和分子,有助于科学家设计和开发针对癌症的靶向策略。多种靶向凋亡相关的肿瘤坏死因子相关凋亡诱导配体(TRAIL)、Bcl-2和蛋白酶体途径的药物已进入II/III期临床试验。首个雷帕霉素靶蛋白(mTOR)抑制剂替西罗莫司已获美国食品药品监督管理局(FDA)批准用于治疗晚期肾细胞癌,预计未来几年会有更多mTOR抑制剂上市。目前正在研究通过使用促自噬剂或自噬抑制剂来应对各种癌症中异常自噬活动的策略。本综述旨在讨论针对凋亡和自噬信号通路的最新抗肿瘤策略以及上述药物临床试验的最新结果。

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