Teicher B A
Dana-Farber Cancer Institute, Boston, MA 02115.
Cancer Metastasis Rev. 1994 Jun;13(2):139-68. doi: 10.1007/BF00689633.
Biologically and therapeutically important hypoxia occurs in many solid tumor masses. Hypoxia can be a direct cause of therapeutic resistance because some drugs and radiation require oxygen to be maximally cytotoxic. Cellular metabolism is altered under hypoxic conditions. Hypoxia can result in drug resistance indirectly if under this condition cells more effectively detoxify the drug molecules. Finally, there is evidence that hypoxia can enhance genetic instability in tumor cells thus allowing more rapid development of drug resistance cells. The current review describes the effects of hypoxia on tumor response to a variety of anti-cancer agents and also describes progress toward therapeutically useful methods of delivering oxygen to tumors in an effort to overcome therapeutic resistance due to hypoxia. Finally, the use of hypoxic cell selective cytotoxic agents as a means of addressing hypoxic 'drug resistance' is discussed.
许多实体肿瘤块中都会出现具有生物学和治疗学重要意义的缺氧情况。缺氧可能是治疗耐药性的直接原因，因为一些药物和辐射需要氧气才能发挥最大的细胞毒性作用。在缺氧条件下，细胞代谢会发生改变。如果在这种情况下细胞能更有效地使药物分子解毒，那么缺氧可能间接导致耐药性。最后，有证据表明缺氧会增强肿瘤细胞中的基因不稳定性，从而使耐药细胞更快地产生。本综述描述了缺氧对肿瘤对多种抗癌药物反应的影响，还描述了在向肿瘤输送氧气以克服缺氧引起的治疗耐药性的治疗有用方法方面所取得的进展。最后，讨论了使用缺氧细胞选择性细胞毒性药物作为解决缺氧“耐药性”的一种手段。
