Gupta Seema, Farooque Abdullah, Adhikari J S, Singh Saurabh, Dwarakanath B S
Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India.
J Cancer Res Ther. 2009 Sep;5 Suppl 1:S16-20. doi: 10.4103/0973-1482.55135.
The development of an approach based on the energy-linked modification of DNA repair and cellular recovery processes using 2-deoxy-D-glucose (2-DG; inhibitor of glycolytic ATP production) has shown promising results in a number of model systems of cancer. Following encouraging results on the tolerance and toxicity (acute as well as late effects) of the combination (2-DG and hypofractionated radiotherapy) in Phase I and II clinical trials, its efficacy is currently under evaluation in Phase III clinical trials for glioma patients. Since heterogeneous physiologic and metabolic status in tumors as well as host-tumor interactions influence the local tumor control, which coupled with systemic disturbances could determine the cure (long-term tumor free survival), investigations on the in vivo responses of tumors to the combined treatment have received considerable attention. This communication provides a brief overview on the in vivo studies related to radio- and chemosensitization of tumors by 2-DG, besides the normal tissue toxicity induced by the combined treatment of 2-DG and radiation or chemotherapeutic drugs.
基于使用2-脱氧-D-葡萄糖(2-DG;糖酵解ATP产生的抑制剂)对DNA修复和细胞恢复过程进行能量关联修饰的方法,已在多种癌症模型系统中显示出有前景的结果。在I期和II期临床试验中,关于联合治疗(2-DG与超分割放疗)的耐受性和毒性(急性及晚期效应)取得令人鼓舞的结果后,其疗效目前正在针对胶质瘤患者的III期临床试验中进行评估。由于肿瘤中异质性的生理和代谢状态以及宿主-肿瘤相互作用会影响局部肿瘤控制,而这与全身紊乱相结合可能决定治愈情况(长期无瘤生存),因此关于肿瘤对联合治疗的体内反应的研究受到了相当大的关注。本通讯除了介绍2-DG与放疗或化疗药物联合治疗所诱导的正常组织毒性外,还简要概述了与2-DG对肿瘤的放射增敏和化学增敏相关的体内研究。