Gatenby Robert A, Gillies Robert J
Department of Radiology, University of Arizona, University Medical Center, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
Int J Biochem Cell Biol. 2007;39(7-8):1358-66. doi: 10.1016/j.biocel.2007.03.021. Epub 2007 Apr 4.
Clinical imaging of primary and metastatic cancers with Fluoro deoxy-d-Glucose Positron Emission Tomography (FdG PET) has clearly demonstrated that increased glucose flux compared to normal tissue is a common trait of human malignancies (Gambhir, 2002) This is a consequence of a shift of glucose metabolism to less efficient glycolytic pathways in response to regional hypoxia and evolution of aerobic glycolysis in many cancer phenotypes. This distinctive metabolic profile presents an inviting target for cancer treatment and prevention. Here, we summarize the therapeutic strategies under investigation to exploit or interrupt tumor glycolytic metabolism. Although a number of approaches are under investigation, none has been sufficiently successful to warrant widespread clinical application. We point out that the environmental heterogeneity and evolutionary capacity of tumor cells that likely led to development of upregulated glycolysis could also promote adaptive strategies that confer resistance to therapies designed to inhibit glucose metabolism.
利用氟代脱氧 - d - 葡萄糖正电子发射断层扫描（FdG PET）对原发性和转移性癌症进行的临床成像已清楚表明，与正常组织相比，葡萄糖通量增加是人类恶性肿瘤的一个共同特征（甘比尔，2002年）。这是葡萄糖代谢向效率较低的糖酵解途径转变的结果，该转变是对局部缺氧的反应以及许多癌症表型中需氧糖酵解演变的结果。这种独特的代谢特征为癌症治疗和预防提供了一个诱人的靶点。在此，我们总结了正在研究的利用或中断肿瘤糖酵解代谢的治疗策略。尽管有多种方法正在研究中，但尚无一种方法足够成功到可保证广泛临床应用。我们指出，可能导致糖酵解上调的肿瘤细胞的环境异质性和进化能力也可能促进适应性策略，从而赋予对旨在抑制葡萄糖代谢的疗法的抗性。
