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BRCA2突变状态作为胰腺癌诊断、预测和预后生物标志物的作用。

The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer.

作者信息

Martinez-Useros Javier, Garcia-Foncillas Jesus

机构信息

Translational Oncology Division, Oncohealth Institute, Health Research Institute, University Hospital Fundación Jiménez Díaz-UAM, Madrid, Spain.

出版信息

Biomed Res Int. 2016;2016:1869304. doi: 10.1155/2016/1869304. Epub 2016 Dec 18.

Abstract

Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation in gene. mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carrying mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to target The present systematic review collects and analyses the role of alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

摘要

胰腺癌是全球最致命的癌症之一,确诊后的预期寿命通常较短。大多数胰腺肿瘤是散发性出现的,并且与吸烟、大量饮酒、高碳水化合物和高糖摄入等习惯高度相关。其他观察性研究表明胰腺癌与接触砷、铅或镉之间存在关联。除了这些因素外,慢性胰腺炎和糖尿病也被认为是这类肿瘤的危险因素。研究发现,10%的胰腺癌病例源于与某些基因改变相关的遗传综合征。其中一种改变包括基因中的突变。这些突变通过直接调控RAD51损害DNA损伤反应和同源重组。鉴于这些将遗传因素与肿瘤发展联系起来的发现,已提出DNA损伤剂作为携带突变的胰腺癌患者的靶向治疗方法。其中一些药物包括铂类药物和PARP抑制剂。然而,对PARP抑制剂的获得性耐药性使得需要新的化疗策略来靶向。本系统综述收集并分析了改变在与家族性癌症相关的遗传综合征早期诊断中的作用,以及作为胰腺癌患者管理的预后和预测生物标志物的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9e/5203890/cb383d264db5/BMRI2016-1869304.001.jpg

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