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胃肠道肿瘤免疫治疗的全面综述,重点关注与PARP抑制剂联合治疗的作用。

A comprehensive review of immunotherapy in gastrointestinal tumors with a focus on the role of combination therapy with PARP inhibitors.

作者信息

Jasim Saade Abdalkareem, Gupta Jitendra, Uthirapathy Subasini, R Roopashree, Kazmi Syeda Wajida, Rizaev Jasur Alimdjanovich, Eldesoqui Mamdouh, Shallan Maythum Ali, Mustafa Yasser Fakri, Hosseen Beneen

机构信息

Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-Maarif, Anbar, Iraq.

Institute of Pharmaceutical Research, GLA University, U. P, Mathura, Pin Code 281406, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 9. doi: 10.1007/s00210-025-04336-z.

Abstract

Defects in the DNA damage response (DDR) can cause genomic instability, leading to genetic mutations or abnormalities that promote cancer growth and progression. Gastrointestinal (GI) cancers are lagging behind other types of tumors in terms of customized therapy with targeted drugs. PARP inhibitors (PARPi) were the first approved cancer treatments to target the DNA damage response in BRCA1/2-mutated breast and ovarian malignancies. Since then, our understanding of the processes underlying tumor sensitization to PARP inhibitors has advanced significantly, as has the use of PARP inhibitors to treat various additional cancer types. Existing methods for assessing the sensitivity of gastrointestinal malignancies to PARP inhibitors rely on extrapolations from other cancer types, regardless of the inconsistency in defining homologous recombination (HR) status across tumor types. Due to the pressing clinical demand, it is critical to have a better knowledge of the therapeutic consequences of DDR alterations in gastrointestinal cancers. Today, combination therapy is used as an effective treatment method in the treatment of cancers. This article attempts to summarize and present the latest findings on the combination therapy of gastrointestinal cancers using PARP inhibitors and other products, especially immunotherapy ones.

摘要

DNA损伤反应(DDR)缺陷可导致基因组不稳定,进而引发促进癌症生长和进展的基因突变或异常。在使用靶向药物进行定制治疗方面,胃肠道(GI)癌落后于其他类型的肿瘤。PARP抑制剂(PARPi)是首批获批用于治疗BRCA1/2突变的乳腺癌和卵巢恶性肿瘤中DNA损伤反应的癌症治疗药物。从那时起,我们对肿瘤对PARP抑制剂敏感化过程的理解有了显著进展,PARP抑制剂在治疗各种其他癌症类型中的应用也是如此。现有的评估胃肠道恶性肿瘤对PARP抑制剂敏感性的方法依赖于从其他癌症类型推断,而忽略了不同肿瘤类型在定义同源重组(HR)状态方面的不一致性。由于迫切的临床需求,深入了解胃肠道癌症中DDR改变的治疗后果至关重要。如今,联合治疗被用作癌症治疗的一种有效方法。本文试图总结并介绍使用PARP抑制剂和其他产品,特别是免疫治疗产品进行胃肠道癌症联合治疗的最新发现。

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