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癌症化疗耐药中的线粒体功能障碍。

Mitochondrial dysfunction in cancer chemoresistance.

机构信息

Institute of Biomembranes and Bioenergetics, Via Amendola 165/A, 70126 Bari, Italy.

Institute of Biomembranes and Bioenergetics, Via Amendola 165/A, 70126 Bari, Italy.

出版信息

Biochem Pharmacol. 2014 Nov 1;92(1):62-72. doi: 10.1016/j.bcp.2014.07.027. Epub 2014 Aug 12.

Abstract

Mitochondrial dysfunction has been associated with cancer development and progression. Recent evidences suggest that pathogenic mutations or depletion of the mitochondrial genome can contribute to development of chemoresistance in malignant tumors. In this review we will describe the current knowledge on the role of mitochondrial dysfunction in the development of chemoresistance in cancer. We will also discuss the significance of this research topic in the context of development of more effective, targeted therapeutic modalities and diagnostic strategies for cancer patients, with a particular focus on the potential use of PARP inhibitors in cancer patients displaying mitochondrial DNA mutations. We will discuss recent studies highlighting the importance of the cross-talk between the tumor microenvironment and mitochondrial functionality in determining selective response to certain chemotherapeutic drugs. Finally, owing to the similarities between cancer and yeast cell metabolism, we will point out the use of yeast as a model system to study cancer-related genes and for anti-cancer drugs screening.

摘要

线粒体功能障碍与癌症的发生和发展有关。最近的证据表明,线粒体基因组的致病突变或耗竭可能导致恶性肿瘤的化疗耐药性的发展。在这篇综述中,我们将描述线粒体功能障碍在癌症化疗耐药性发展中的作用的现有知识。我们还将讨论这一研究课题在开发更有效、有针对性的治疗方法和癌症患者诊断策略方面的意义,特别关注在显示线粒体 DNA 突变的癌症患者中使用 PARP 抑制剂的潜力。我们将讨论最近的研究,强调肿瘤微环境与线粒体功能之间的相互作用在决定对某些化疗药物的选择性反应中的重要性。最后,由于癌症和酵母细胞代谢之间存在相似性,我们将指出使用酵母作为模型系统来研究与癌症相关的基因和筛选抗癌药物的用途。

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