Brown J M
Mayer Cancer Biology Laboratory, Department of Radiation Oncology, Stanford University School of Medicine, CA 94305-5468, USA.
Br J Cancer. 1998 Jun;77 Suppl 4(Suppl 4):12-4. doi: 10.1038/bjc.1998.430.
Human solid tumours are composed of a significant proportion of hypoxic cells, i.e. cells with oxygen levels lower than those of normal tissues. Tumour hypoxic cells have been shown to have a negative impact on the response of solid tumours to radiation therapy and chemotherapy. However, these low cellular oxygen levels can be exploited by a drug that is specifically activated to a cytotoxic metabolite at these low levels. Tirapazamine is a novel bioreductive agent with selective cytotoxicity to hypoxic tumour cells, irrespective of their p53 status or apoptotic response, and acts synergistically with cisplatin. This potentiation is dependent on an interaction that can only take place in a hypoxic environment, resulting in a significant sensitization of the cells to cisplatin cell killing, with no increase in the systemic toxicity of cisplatin. Thus, the low cellular oxygen levels common in solid tumours can be turned from disadvantage to advantage using the hypoxia-selective cytotoxic drug tirapazamine.
人类实体瘤由相当比例的缺氧细胞组成，即氧水平低于正常组织的细胞。肿瘤缺氧细胞已被证明对实体瘤对放射治疗和化疗的反应有负面影响。然而，这些低细胞氧水平可被一种在这些低水平下特异性激活为细胞毒性代谢物的药物所利用。替拉扎明是一种新型生物还原剂，对缺氧肿瘤细胞具有选择性细胞毒性，无论其p53状态或凋亡反应如何，并与顺铂协同作用。这种增强作用取决于一种只能在缺氧环境中发生的相互作用，导致细胞对顺铂细胞杀伤的显著敏化，而顺铂的全身毒性没有增加。因此，使用缺氧选择性细胞毒性药物替拉扎明，实体瘤中常见的低细胞氧水平可以从劣势转变为优势。
