Demény Máté A, Virág László
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
MTA-DE Cell Biology and Signaling Research Group, 4032 Debrecen, Hungary.
Cancers (Basel). 2021 Apr 24;13(9):2057. doi: 10.3390/cancers13092057.
Poly (ADP-ribose) polymerases (PARPs) modify target proteins with a single ADP-ribose unit or with a poly (ADP-ribose) (PAR) polymer. PARP inhibitors (PARPis) recently became clinically available for the treatment of BRCA1/2 deficient tumors via the synthetic lethality paradigm. This personalized treatment primarily targets DNA damage-responsive PARPs (PARP1-3). However, the biological roles of PARP family member enzymes are broad; therefore, the effects of PARPis should be viewed in a much wider context, which includes complex effects on all known hallmarks of cancer. In the companion paper (part 1) to this review, we presented the fundamental roles of PARPs in intrinsic cancer cell hallmarks, such as uncontrolled proliferation, evasion of growth suppressors, cell death resistance, genome instability, replicative immortality, and reprogrammed metabolism. In the second part of this review, we present evidence linking PARPs to cancer-associated inflammation, anti-cancer immune response, invasion, and metastasis. A comprehensive overview of the roles of PARPs can facilitate the identification of novel cancer treatment opportunities and barriers limiting the efficacy of PARPi compounds.
聚（ADP-核糖）聚合酶（PARP）通过单个ADP-核糖单元或聚（ADP-核糖）（PAR）聚合物修饰靶蛋白。PARP抑制剂（PARPi）最近通过合成致死模式在临床上可用于治疗BRCA1/2缺陷型肿瘤。这种个性化治疗主要针对DNA损伤反应性PARP（PARP1-3）。然而，PARP家族成员酶的生物学作用广泛；因此，PARPi的作用应在更广泛的背景下看待，这包括对所有已知癌症标志的复杂影响。在本综述的配套论文（第1部分）中，我们阐述了PARP在癌细胞固有标志中的基本作用，如不受控制的增殖、逃避生长抑制、细胞死亡抗性、基因组不稳定、复制永生和代谢重编程。在本综述的第二部分，我们提供了将PARP与癌症相关炎症、抗癌免疫反应、侵袭和转移联系起来的证据。对PARP作用的全面概述有助于识别新的癌症治疗机会以及限制PARPi化合物疗效的障碍。
