BRCA 突变型胰腺导管腺癌。
BRCA-mutant pancreatic ductal adenocarcinoma.
机构信息
Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy.
Medical Oncology Unit, Sapienza University of Rome, Rome, Italy.
出版信息
Br J Cancer. 2021 Nov;125(10):1321-1332. doi: 10.1038/s41416-021-01469-9. Epub 2021 Jul 14.
Abstract
Despite continued research, pancreatic ductal adenocarcinoma (PDAC) remains one of the main causes of cancer death. Interest is growing in the role of the tumour suppressors breast cancer 1 (BRCA1) and BRCA2-typically associated with breast and ovarian cancer-in the pathogenesis of PDAC. Indeed, both germline and sporadic mutations in BRCA1/2 have been found to play a role in the development of PDAC. However, data regarding BRCA1/2-mutant PDAC are lacking. In this review, we aim to outline the specific landscape of BRCA-mutant PDAC, focusing on heritability, clinical features, differences between BRCA1 and 2 mutations and between germline and sporadic alterations, as well as established therapeutic strategies and those that are still under evaluation.
摘要
尽管不断有研究，但胰腺导管腺癌 (PDAC) 仍然是癌症死亡的主要原因之一。人们对肿瘤抑制因子乳腺癌 1 (BRCA1) 和 BRCA2 的作用越来越感兴趣——它们通常与乳腺癌和卵巢癌有关——在 PDAC 的发病机制中。事实上，BRCA1/2 的种系和散发性突变已被发现与 PDAC 的发展有关。然而，关于 BRCA1/2 突变型 PDAC 的数据仍然缺乏。在这篇综述中，我们旨在概述 BRCA 突变型 PDAC 的特定特征，重点关注遗传性、临床特征、BRCA1 和 2 突变之间以及种系和散发性改变之间的差异，以及已确立的治疗策略和仍在评估中的策略。
相似文献
1
BRCA-mutant pancreatic ductal adenocarcinoma.BRCA 突变型胰腺导管腺癌。
Br J Cancer. 2021 Nov;125(10):1321-1332. doi: 10.1038/s41416-021-01469-9. Epub 2021 Jul 14.
2
BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts.在高危胰腺癌筛查队列和胰腺癌队列中，经常能检测到BRCA1和BRCA2种系突变。
Cancer. 2014 Jul 1;120(13):1960-7. doi: 10.1002/cncr.28662. Epub 2014 Apr 15.
3
Risk of pancreatic ductal adenocarcinoma associated with carriage of BRCA1 and/or BRCA2 mutation: A systematic review and meta-analysis.BRCA1 和/或 BRCA2 基因突变携带者患胰腺导管腺癌的风险：系统评价和荟萃分析。
J Surg Oncol. 2022 Nov;126(6):1028-1037. doi: 10.1002/jso.26994. Epub 2022 Jun 30.
4
Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma.胚系 BRCA 突变在大型基于临床的胰腺导管腺癌患者队列中的研究。
J Clin Oncol. 2015 Oct 1;33(28):3124-9. doi: 10.1200/JCO.2014.59.7401. Epub 2015 May 4.
5
Pancreatic acinar cell carcinoma is associated with germline mutations: a case report and literature review.胰腺腺泡细胞癌与种系突变相关：病例报告及文献复习。
Cancer Biol Ther. 2019;20(7):949-955. doi: 10.1080/15384047.2019.1595274. Epub 2019 Apr 19.
6
The role of PARP inhibitors in germline BRCA-associated pancreatic ductal adenocarcinoma.聚腺苷二磷酸核糖聚合酶抑制剂在种系 BRCA 相关胰腺导管腺癌中的作用。
Clin Adv Hematol Oncol. 2020 Mar;18(3):168-179.
7
Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing.亚洲胰腺腺癌患者胚系 BRCA 突变：评估遗传检测风险类别的前瞻性研究。
Invest New Drugs. 2018 Feb;36(1):163-169. doi: 10.1007/s10637-017-0497-1. Epub 2017 Aug 7.
8
Outcome of Pancreatic Cancer Surveillance Among High-Risk Individuals Tested for Germline Mutations in and .种系基因突变 和 检测的高危个体的胰腺癌监测结果
Cancer Prev Res (Phila). 2019 Sep;12(9):599-608. doi: 10.1158/1940-6207.CAPR-18-0272. Epub 2019 Jul 23.
9
Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants.携带胚系 BRCA1-2 致病性变异的胰腺癌患者的治疗机会和未来展望。
Cancer Treat Rev. 2021 Nov;100:102262. doi: 10.1016/j.ctrv.2021.102262. Epub 2021 Jul 23.
10
Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation.携 BRCA1/2、MLH1 和 APC 基因突变的胰腺癌：表型相关性和新型种系 BRCA2 突变的检测。
Genes (Basel). 2022 Feb 9;13(2):321. doi: 10.3390/genes13020321.
引用本文的文献
1
Radiogenomics of Stereotactic Radiotherapy: Genetic Mechanisms Underlying Radiosensitivity, Resistance, and Immune Response.立体定向放射治疗的放射基因组学：放射敏感性、抗性和免疫反应背后的遗传机制。
Genes (Basel). 2025 Jun 24;16(7):732. doi: 10.3390/genes16070732.
2
Proteomics in pancreatic cancer.胰腺癌中的蛋白质组学
Biomark Res. 2025 Jul 6;13(1):93. doi: 10.1186/s40364-025-00805-y.
3
and drive metabolic reprogramming in pancreatic cancer cells: the influence of oxidative and nitrosatice stress.并驱动胰腺癌细胞的代谢重编程：氧化应激和亚硝化应激的影响
Front Cell Dev Biol. 2025 Jun 11;13:1547582. doi: 10.3389/fcell.2025.1547582. eCollection 2025.
4
A first-in-class inhibitor of homologous recombination DNA repair counteracts tumour growth, metastasis and therapeutic resistance in pancreatic cancer.一种一流的同源重组DNA修复抑制剂可对抗胰腺癌的肿瘤生长、转移和治疗抗性。
J Exp Clin Cancer Res. 2025 Apr 24;44(1):129. doi: 10.1186/s13046-025-03389-5.
5
Pancreatic Cancer: Pathogenesis and Clinical Studies.胰腺癌：发病机制与临床研究
MedComm (2020). 2025 Apr 2;6(4):e70162. doi: 10.1002/mco2.70162. eCollection 2025 Apr.
6
Claudin 18 (43-14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy.Claudin 18（43-14A克隆体）在胰腺导管腺癌中的表达：评估zolbetuximab治疗的潜在临床生物标志物
Transl Oncol. 2025 May;55:102362. doi: 10.1016/j.tranon.2025.102362. Epub 2025 Mar 20.
7
Targeting BARD1 suppresses a Myc-dependent transcriptional program and tumor growth in pancreatic ductal adenocarcinoma.靶向BARD1可抑制胰腺导管腺癌中Myc依赖性转录程序和肿瘤生长。
Neoplasia. 2025 May;63:101152. doi: 10.1016/j.neo.2025.101152. Epub 2025 Mar 16.
8
Hereditary Pancreatic Cancer: Advances in Genetic Testing, Early Detection Strategies, and Personalized Management.遗传性胰腺癌：基因检测、早期检测策略及个性化管理的进展
J Clin Med. 2025 Jan 9;14(2):367. doi: 10.3390/jcm14020367.
9
BRCA1 & BRCA2 methylation as a prognostic and predictive biomarker in cancer: Implementation in liquid biopsy in the era of precision medicine.BRCA1和BRCA2甲基化作为癌症的预后和预测生物标志物：在精准医学时代液体活检中的应用
Clin Epigenetics. 2024 Dec 6;16(1):178. doi: 10.1186/s13148-024-01787-8.
10
The role of epigenetic regulation in pancreatic ductal adenocarcinoma progression and drug response: an integrative genomic and pharmacological prognostic prediction model.表观遗传调控在胰腺导管腺癌进展和药物反应中的作用：一种整合基因组学和药理学的预后预测模型。
Front Pharmacol. 2024 Nov 21;15:1498031. doi: 10.3389/fphar.2024.1498031. eCollection 2024.
本文引用的文献
1
Reflex Testing for Germline , , , and Mutations in Pancreatic Cancer: Mutation Prevalence and Clinical Outcomes From Two Canadian Research Registries.胰腺癌种系、、、和突变的反射试验：来自两个加拿大研究登记处的突变患病率和临床结果
JCO Precis Oncol. 2018 Nov;2:1-16. doi: 10.1200/PO.17.00098.
2
Retrospective Survival Analysis of Patients With Advanced Pancreatic Ductal Adenocarcinoma and Germline or Mutations.晚期胰腺导管腺癌伴种系或体细胞突变患者的回顾性生存分析
JCO Precis Oncol. 2018 Nov;2:1-9. doi: 10.1200/PO.17.00152.
3
Retrospective Survival Analysis of Patients With Resected Pancreatic Ductal Adenocarcinoma and a Germline or Mutation.接受切除的胰腺导管腺癌合并种系或体细胞突变患者的回顾性生存分析
JCO Precis Oncol. 2019 Dec;3:1-11. doi: 10.1200/PO.18.00271.
4
Randomized Phase II Study of PARP Inhibitor ABT-888 (Veliparib) with Modified FOLFIRI versus FOLFIRI as Second-line Treatment of Metastatic Pancreatic Cancer: SWOG S1513.随机、二期研究 PARP 抑制剂 ABT-888（维利帕尼）联合改良 FOLFIRI 方案对比 FOLFIRI 方案二线治疗转移性胰腺癌：SWOG S1513
Clin Cancer Res. 2021 Dec 1;27(23):6314-6322. doi: 10.1158/1078-0432.CCR-21-1789. Epub 2021 Sep 27.
5
Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in , , or .铂敏感的晚期胰腺癌且存在种系或体细胞致病变体的患者中，维持使用鲁卡帕尼的II期研究。 （注：原文中“in , , or .”部分内容缺失，以上是按完整句子结构翻译的大致内容）
J Clin Oncol. 2021 Aug 1;39(22):2497-2505. doi: 10.1200/JCO.21.00003. Epub 2021 May 10.
6
Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance.聚腺苷二磷酸核糖聚合酶抑制剂的治疗选择途径和潜在耐药机制。
Exp Mol Med. 2021 Jan;53(1):42-51. doi: 10.1038/s12276-021-00557-3. Epub 2021 Jan 25.
7
A novel somatic BRCA2 point mutation in a metastatic pancreatic cancer patient: a case report.一名转移性胰腺癌患者中存在新型种系 BRCA2 点突变：病例报告。
BMC Med Genomics. 2021 Jan 6;14(1):6. doi: 10.1186/s12920-020-00850-6.
8
Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.遗传/家族性高风险评估：乳腺癌、卵巢癌和胰腺癌，第 2.2021 版，NCCN 肿瘤学临床实践指南。
J Natl Compr Canc Netw. 2021 Jan 6;19(1):77-102. doi: 10.6004/jnccn.2021.0001.
9
Update on the Role of Poly (ADP-Ribose) Polymerase Inhibitors in the DNA Repair-Deficient Pancreatic Cancers: A Narrative Review.聚（ADP-核糖）聚合酶抑制剂在DNA修复缺陷型胰腺癌中的作用进展：一项叙述性综述
J Pancreat Cancer. 2020 Dec 4;6(1):107-115. doi: 10.1089/pancan.2020.0010. eCollection 2020.
10
Molecular characteristics of and mutations in pancreatic ductal adenocarcinoma.胰腺导管腺癌中 和 突变的分子特征。
ESMO Open. 2020 Nov;5(6):e000942. doi: 10.1136/esmoopen-2020-000942.
Zotero 插件