Is autophagy induction by PARP inhibitors a target for therapeutic benefit?
Is autophagy induction by PARP inhibitors a target for therapeutic benefit?
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DOI：
10.32604/or.2022.026459
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发表时间：
2022
影响因子：
3.1
通讯作者：
Gewirtz, David A.
中科院分区：
文献类型：
--
作者：
Elshazly, Ahmed M.;Nguyen, Tuong Vi V.;Gewirtz, David A.
PARP抑制剂已被证明与常规治疗剂联合治疗各种实体瘤以及血液恶性肿瘤是有效的，特别是当肿瘤在DNA修复途径中有缺陷时。然而，与其他化学治疗剂的情况一样，它们的有效性经常因耐药性的发展而受到损害。PARP抑制剂一直被报道促进自噬，自噬是一种通过降解和再利用受损的亚细胞器和蛋白质来维持细胞稳态并充当能量来源的过程。自噬可以表现出不同的功能特性，最突出的是细胞保护。此外，细胞毒性和非保护性功能形式也已确定。在这篇综述中，我们探讨了现有文献中关于自噬在临床使用的PARP抑制剂中的不同作用，强调了靶向自噬作为辅助治疗的可能性，以潜在地增加PARP抑制的有效性并克服耐药性的发展。
PARP inhibitors have proven to be effective in conjunction with conventional therapeutics in the treatment of various solid as well as hematologic malignancies, particularly when the tumors are deficient in DNA repair pathways. However, as the case with other chemotherapeutic agents, their effectiveness is often compromised by the development of resistance. PARP inhibitors have consistently been reported to promote autophagy, a process that maintains cellular homeostasis and acts as an energy source by the degradation and reutilization of damaged subcellular organelles and proteins. Autophagy can exhibit different functional properties, the most prominent being cytoprotective. In addition, both cytotoxic and non-protective functions forms have also been identified. In this review, we explore the available literature regarding the different roles of autophagy in response to clinically-used PARP inhibitors, highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of PARP inhibition and to overcome the development of resistance.
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影响因子：
5
作者：
Ji, Yunxiang;Wang, Qian;Ye, Li
通讯作者：
Ye, Li
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
3.4
作者：
Alotaibi M;Sharma K;Saleh T;Povirk LF;Hendrickson EA;Gewirtz DA
通讯作者：
Gewirtz DA
影响因子：
--
作者：
Bhutia, Sujit K.;Mukhopadhyay, Subhadip;Sinha, Niharika;Das, Durgesh Nandini;Panda, Prashanta Kumar;Patra, Samir K.;Maiti, Tapas K.;Mandal, Mahitosh;Dent, Paul;Wang, Xiang-Yang;Das, Swadesh K.;Sarkar, Devanand;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
具有转移性cast割前列腺癌的男性的鲁卡巴里（Rucaparib）具有BRCA1或BRCA2基因改变。
DOI：
10.1200/jco.20.01035
发表时间：
2020-11-10
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Abida W;Patnaik A;Campbell D;Shapiro J;Bryce AH;McDermott R;Sautois B;Vogelzang NJ;Bambury RM;Voog E;Zhang J;Piulats JM;Ryan CJ;Merseburger AS;Daugaard G;Heidenreich A;Fizazi K;Higano CS;Krieger LE;Sternberg CN;Watkins SP;Despain D;Simmons AD;Loehr A;Dowson M;Golsorkhi T;Chowdhury S;TRITON2 investigators
通讯作者：
TRITON2 investigators