Oxygen delivery: implications for the biology and therapy of solid tumors.
Oxygen delivery: implications for the biology and therapy of solid tumors.
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作者：
S. Rockwell
实体恶性肿瘤在其发展的早期阶段发展为缺氧区域，而它们的大小仍然是微观的，在它们开始血管生成之前。缺氧的生理效应和相关的微环境不足增加了突变率，选择了正常程序性细胞死亡途径中缺乏的细胞，并促进了越来越多的侵袭性、转移性表型的发展。低氧肿瘤细胞对辐射和许多抗肿瘤药物也有耐药性，并限制了实体瘤放疗和化疗的治愈率。本文综述了几种改善肿瘤氧合的方法，并讨论了实验室和临床研究的结果，以检验它们在改善放射治疗结果方面的疗效。过去的临床试验，使用非最佳药物和方案来规避缺氧的保护作用，将局部控制率提高了约10%。当正在进行实验室测试的新药物用于优化设计的临床方案时，应该有更大的改进。
Solid malignancies develop areas of hypoxia during the earliest phase of their development, while they are still microscopic in size and before they have initiated angiogenesis. The physiologic effects of hypoxia and the associated microenvironmental inadequacies increase mutation rates, select for cells deficient in normal pathways of programmed cell death, and contribute to the development of an increasingly invasive, metastatic phenotype. Hypoxic tumor cells are also resistant to radiation and to many antineoplastic drugs, and can limit the curability of solid tumors by radiotherapy and chemotherapy. This article reviews several approaches to improving tumor oxygenation and discusses the results of laboratory and clinical studies examining their efficacy in improving the outcome of radiation therapy. Past clinical trials, using nonoptimal agents and regimens to circumvent the protective effects of hypoxia, improved local control rates by approximately 10%. Greater improvements should be possible when the new agents now undergoing laboratory testing are used in optimally designed clinical regimens.