Research Progress of M6A Methylation Modification in Immunotherapy of Colorectal Cancer.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-03-06 DOI:10.2174/0115680096332984250221071109

Jingfan Zheng, Yuyu Chen, Xintong Peng, Wei Zheng, Yu Zhang, Fengrong Hei, Zhong Lu

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引用次数: 0

Abstract

Among the Poly(ADP-ribose) Polymerase (PARP) family in mammals, PARP1 is the first identified and well-studied member that plays a critical role in DNA damage repair and has been proven to be an effective target for cancer therapy. Here, we have reviewed not only the role of PARP1 in different DNA damage repair pathways, but also the working mech-anisms of several PARP inhibitors (PARPi), inhibiting Poly-ADP-ribosylation (PARylation) processing and PAR chains production to trap PARP1 on impaired DNA and inducing Tran-scription-replication Conflicts (TRCs) by inhibiting the PARP1 activity. This review has sys-tematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer. Furthermore, probable challenges in PARPi application and drug resistance mechanisms have also been discussed. Despite these challenges, further development of new PARP1 inhibitors appears promising as a valuable approach to cancer treatment.

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M6A甲基化修饰在结直肠癌免疫治疗中的研究进展

在哺乳动物聚（adp -核糖）聚合酶（PARP）家族中，PARP1是第一个被发现并得到充分研究的成员，它在DNA损伤修复中起着关键作用，并已被证明是癌症治疗的有效靶点。在这里，我们不仅回顾了PARP1在不同DNA损伤修复途径中的作用，而且还回顾了几种PARP抑制剂（PARPi）的工作机制，它们抑制poly - adp核糖基化（PARylation）加工和PAR链的产生，从而将PARP1捕获在受损DNA上，并通过抑制PARP1活性诱导转录复制冲突（TRCs）。本文系统总结了奥拉帕尼、鲁卡帕尼、尼拉帕尼、塔拉唑帕尼、福唑帕尼、帕米帕尼等6种获批PARPi在不同类型肿瘤的单药及联合化疗、放疗、免疫治疗中的最新临床应用。此外，还讨论了PARPi应用中可能面临的挑战和耐药机制。尽管存在这些挑战，新的PARP1抑制剂的进一步开发似乎有望成为一种有价值的癌症治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.