Bioenergetics pathways and therapeutic resistance in gliomas: emerging role of mitochondria.
Bioenergetics pathways and therapeutic resistance in gliomas: emerging role of mitochondria.
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DOI：
10.2174/138161211797249251
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发表时间：
2011-07
影响因子：
3.1
通讯作者：
Corinne E. Griguer;C. Oliva
中科院分区：
文献类型：
--
作者：
Corinne E. Griguer;C. Oliva
癌症代谢已经获得了相当大的兴趣，因为重要的研究已经表明各种癌基因的激活和细胞代谢的改变之间的密切关系。此外，一些证据表明，代谢成像可以显着影响恶性胶质瘤患者的管理和监测肿瘤对治疗的反应。在这种情况下，线粒体在细胞能量产生、细胞凋亡和自由基产生中发挥核心作用。线粒体功能障碍与许多癌症的发展有关，包括脑肿瘤。多形性胶质母细胞瘤（GBM）是最常见的原发性颅内肿瘤，其几乎一致的致死率为12-15个月的中位生存期。目前的管理包括手术，放疗和化疗的组合。尽管有积极的治疗方法，但90%的GBM患者会复发。这种不良结果的一个原因是多药耐药（MDR）表型的发展。我们和其他人已经详细描述了神经胶质瘤生长和进展的生物能量途径。最引人注目的观察结果之一是，依赖于糖酵解代谢的胶质瘤细胞通过参与其线粒体途径容易地适应生物能应激，以便存活和生长。这表明线粒体功能在神经胶质瘤的生物学中起着关键作用。尽管如此，线粒体功能在恶性脑肿瘤中化学抗性的发展中的作用在很大程度上是未知的。我们的目的是在这篇综述中描述目前的知识线粒体功能的作用，在胶质瘤化疗耐药的发展。重点将放在ABC运输机上。我们将讨论这些研究领域的意义的背景下，更有效的，有针对性的治疗方式和诊断策略的恶性胶质瘤患者的发展。
Cancer metabolism has gained considerable interest, since significant studies have indicated a close relationship between the activation of various oncogenes and alterations of cellular metabolism. Furthermore, several lines of evidence have shown that metabolic imaging can significantly impact malignant glioma patient management and monitoring of tumor response to therapy. In this context, mitochondria play a central role in cellular energy production, apoptosis and free radical generation. Mitochondrial malfunctions have been associated with development of many cancers, including brain tumors. Glioblastoma multiforme (GBM) is the most common primary intracranial neoplasm and its almost uniform lethality is exemplified by a median survival of 12-15 months. Current management consists of a combination of surgery, radiotherapy and chemotherapy. Despite aggressive treatment approaches, recurrence occurs in 90% of GBM patients. One cause of this poor outcome is development of a multidrug-resistance (MDR) phenotype. We and others have described in detail the bioenergetic pathways central to glioma growth and progression. One of the most striking observations is that glioma cells which rely on glycolytic metabolism readily adapt to bioenergetic stress by engaging their mitochondrial pathway in order to survive and grow. This suggests that mitochondrial function plays a critical role in the biology of gliomas. Still, the role that mitochondrial function has in development of chemoresistance in malignant brain tumors is largely unknown. Our goal in this review is to describe the current knowledge on the role of mitochondria function in the development of chemoresistance in glioma. Particular emphasis will be on ABC transporters. We will discuss the significance of these research areas in the context of development of more effective, targeted therapeutic modalities and diagnostic strategies for malignant glioma patients.