Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, China.
Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
Biomed Pharmacother. 2022 Sep;153:113458. doi: 10.1016/j.biopha.2022.113458. Epub 2022 Jul 23.
Since the concept, DNA damage repair has been stated as a natural biological event, and research has increasingly revealed its strong association to tumors, aging, immunity, biochemical detection, and other factors. The discovery of abnormal DNA repair in cancers has been heralded as a paradigm shift in the treatment of malignancies. A poly (ADP-ribose) polymerase (PARP) activates poly (ADP-ribosylation) to repair single-strand DNA breaks after DNA damage. In some cancers, such as breast cancer and gastric cancer, a PARP inhibitor can target the DNA damage response pathway, prevent DNA repair, and induce homologous recombination deficiency (HRD) tumors to create the phenomena of synthetic lethality. Increasingly, clinical trials are being submitted to research the uses of PARP inhibitors in various types of cancers. Small cell lung cancer (SCLC) is a quickly growing malignancy with numerous therapeutic limitations and a dismal prognosis. Sequencing of mutant genes revealed multiple gene connections that may contribute to its carcinogenesis, indicating a viable study direction. Furthermore, the therapy of SCLC with PARP inhibitors has been further explored. The mechanism of PARP action, as well as the advancement of its preclinical and clinical applications in SCLC, will be discussed in this review.
自 DNA 损伤修复的概念被提出以来，它一直被认为是一种自然的生物学事件，并且研究越来越多地揭示了它与肿瘤、衰老、免疫、生化检测等因素的强烈关联。癌症中异常 DNA 修复的发现被视为恶性肿瘤治疗的范式转变。聚（ADP-核糖）聚合酶（PARP）在 DNA 损伤后激活聚（ADP-核糖）化以修复单链 DNA 断裂。在某些癌症中，如乳腺癌和胃癌，PARP 抑制剂可以靶向 DNA 损伤反应途径，阻止 DNA 修复，并诱导同源重组缺陷（HRD）肿瘤产生合成致死现象。越来越多的临床试验正在提交研究 PARP 抑制剂在各种类型癌症中的用途。小细胞肺癌（SCLC）是一种生长迅速的恶性肿瘤，治疗方法有限，预后不佳。突变基因的测序揭示了多个可能导致其癌变的基因联系，表明这是一个可行的研究方向。此外，PARP 抑制剂在 SCLC 中的治疗作用也得到了进一步的探索。本文将讨论 PARP 的作用机制，以及其在 SCLC 中的临床前和临床应用的进展。
