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RAD51作为胰腺癌的潜在生物标志物和治疗靶点。

RAD51 as a potential biomarker and therapeutic target for pancreatic cancer.

作者信息

Nagathihalli Nagaraj S, Nagaraju Ganesh

机构信息

Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-6860, USA.

出版信息

Biochim Biophys Acta. 2011 Dec;1816(2):209-18. doi: 10.1016/j.bbcan.2011.07.004. Epub 2011 Jul 23.

Abstract

Chemotherapy is a very important therapeutic strategy for cancer treatment. The failure of conventional and molecularly targeted chemotherapeutic regimes for the treatment of pancreatic cancer highlights a desperate need for novel therapeutic interventions. Chemotherapy often fails to eliminate all tumor cells because of intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Overexpression of RAD51 protein, a key player in DNA repair/recombination has been observed in many cancer cells and its hyperexpression is implicated in drug resistance. Recent studies suggest that RAD51 overexpression contributes to the development, progression and drug resistance of pancreatic cancer cells. Here we provide a brief overview of the available pieces of evidence in support of the role of RAD51 in pancreatic tumorigenesis and drug resistance, and hypothesize that RAD51 could serve as a potential biomarker for diagnosis of pancreatic cancer. We discuss the possible involvement of RAD51 in the drug resistance associated with epithelial to mesenchymal transition and with cancer stem cells. Finally, we speculate that targeting RAD51 in pancreatic cancer cells may be a novel approach for the treatment of pancreatic cancer.

摘要

化疗是癌症治疗中非常重要的治疗策略。传统化疗方案和分子靶向化疗方案在治疗胰腺癌方面的失败凸显了对新型治疗干预措施的迫切需求。由于内在或获得性耐药,化疗往往无法消除所有肿瘤细胞,这是肿瘤复发最常见的原因。在许多癌细胞中都观察到了DNA修复/重组的关键蛋白RAD51的过表达,其高表达与耐药性有关。最近的研究表明,RAD51过表达促进了胰腺癌细胞的发生、发展和耐药性。在此,我们简要概述支持RAD51在胰腺肿瘤发生和耐药性中作用的现有证据,并推测RAD51可能作为诊断胰腺癌的潜在生物标志物。我们讨论了RAD51可能参与与上皮-间质转化和癌症干细胞相关的耐药性。最后,我们推测靶向胰腺癌细胞中的RAD51可能是治疗胰腺癌的一种新方法。

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