Broad targeting of resistance to apoptosis in cancer.
Broad targeting of resistance to apoptosis in cancer.
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DOI：
10.1016/j.semcancer.2015.03.001
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发表时间：
2015-12
影响因子：
14.5
通讯作者：
Azmi AS
中科院分区：
文献类型：
--
作者：
Mohammad RM;Muqbil I;Lowe L;Yedjou C;Hsu HY;Lin LT;Siegelin MD;Fimognari C;Kumar NB;Dou QP;Yang H;Samadi AK;Russo GL;Spagnuolo C;Ray SK;Chakrabarti M;Morre JD;Coley HM;Honoki K;Fujii H;Georgakilas AG;Amedei A;Niccolai E;Amin A;Ashraf SS;Helferich WG;Yang X;Boosani CS;Guha G;Bhakta D;Ciriolo MR;Aquilano K;Chen S;Mohammed SI;Keith WN;Bilsland A;Halicka D;Nowsheen S;Azmi AS
细胞凋亡或程序性细胞死亡是从体内清除衰老细胞的自然方式。大多数抗癌疗法通过触发细胞凋亡诱导和相关的细胞死亡网络来消除恶性细胞。然而，在癌症中，去调控的凋亡信号，特别是抗凋亡系统的激活，允许癌细胞逃避这一程序，导致不受控制的增殖，从而导致肿瘤存活、治疗抵抗和癌症复发。这种耐药性是一种复杂的现象，是各种分子和信号通路相互作用的结果。在这篇全面的综述中，我们讨论了促进癌症细胞凋亡抵抗的各种因素。本文讨论的主要耐药靶点包括(1)Bcl-2和Mcl-1蛋白；(2)自噬过程；(3)坏死、坏死下垂；(4)热休克蛋白信号；(5)蛋白酶体途径；(6)表观遗传机制；(7)核出口信号异常。强调了当前治疗方式的缺点，并采用了广泛的策略，包括(a)棉酚；(b) epigallocatechin-3-gallate;(c) UMI-77 (d)雷公藤甲素和(e)可用于克服细胞死亡抗性的selinexor。这篇综述为设计成功的抗癌策略提供了路线图，这些策略可以克服对细胞凋亡的抵抗，从而改善癌症患者的治疗效果。
Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer.