Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
Institute of Basic Science-Center for Genomic Integrity, Ulsan, South Korea.
JCO Precis Oncol. 2021 Oct 22;5. doi: 10.1200/PO.21.00152. eCollection 2021.
With the broad use of next-generation sequencing assays, it has become clear that mutations in DNA repair genes are more commonly found than previously reported. In advanced prostate cancer patients with 1/2 or mutations, poly (ADP-ribose) polymerase inhibition (PARPi) causes an increased overall survival advantage compared with patients without these mutations. This review explores the advantages and limitations of PARPi treatment and its use beyond 1/2-altered tumors. Furthermore, it discusses the benefits of current biomarkers and what role functional biomarkers and organoids may play in addressing the involvement of homologous recombination repair mutations in tumor development and progression.
A systematic review was conducted in MEDLINE, National Library of Medicine, and ClinicalTrials.gov to identify studies published between January 1, 2016, and August 31, 2021. The search strategy incorporated terms for PARPi, BRCA, DNA damage, homologous recombination, organoids, patient-derived organoids, biomarker AND prostate cancer, breast cancer, ovarian cancer.
A total of 261 records remained after duplicate removal, 69 of which were included in the qualitative synthesis.
To improve the outcome of targeted therapy and increase sensitivity of tumor detection, patients should be repeatedly screened for DNA repair gene alterations and biomarkers. Future clinical studies should explore the use of PARPi beyond 1/2 mutations and focus on finding new synthetically lethal interactions.
随着下一代测序技术的广泛应用，人们已经清楚地认识到，DNA 修复基因的突变比以前报道的更为常见。在存在 1/2 或 突变的晚期前列腺癌患者中，与没有这些突变的患者相比，多聚（ADP-核糖）聚合酶抑制剂（PARPi）可带来总体生存优势的提高。本综述探讨了 PARPi 治疗的优势和局限性及其在 1/2 改变肿瘤之外的应用。此外，还讨论了当前生物标志物的优势以及功能生物标志物和类器官在解决同源重组修复基因突变在肿瘤发生和发展中的作用。
在 MEDLINE、美国国家医学图书馆和 ClinicalTrials.gov 中进行了系统综述，以确定 2016 年 1 月 1 日至 2021 年 8 月 31 日期间发表的研究。搜索策略纳入了 PARPi、BRCA、DNA 损伤、同源重组、类器官、患者来源的类器官、生物标志物和前列腺癌、乳腺癌、卵巢癌的术语。
在去除重复项后，共保留了 261 条记录，其中 69 条被纳入定性综合分析。
为了提高靶向治疗的效果并提高肿瘤检测的敏感性，应反复对患者进行 DNA 修复基因改变和生物标志物的筛查。未来的临床研究应探讨 PARPi 在 1/2 突变之外的应用，并侧重于寻找新的合成致死相互作用。
