The experimental and clinical rationale for the use of S-phase-specific radiosensitizers to overcome tumor cell repopulation.
The experimental and clinical rationale for the use of S-phase-specific radiosensitizers to overcome tumor cell repopulation.
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使用 S 期特异性放射增敏剂克服肿瘤细胞增殖的实验和临床原理。
作者：
C. Mcginn;T. Kinsella
临床和实验室证据表明，几种常见的人类癌症含有快速增殖的克隆原群体，可能对常规放疗后的局部控制产生重大影响。改善局部控制的策略包括使用S期特异性放射增敏剂，如卤代嘧啶类似物（5-碘脱氧尿苷、5-溴脱氧尿苷、氟脱氧尿苷、5-氟尿嘧啶）和羟基脲。这些药物仅被合成DNA的细胞吸收和代谢，因此增加的肿瘤增殖应导致增加的放射增敏。虽然这些药物的初步临床试验是不确定的，但最近的几份报告重新点燃了人们对这些放射增敏剂的兴趣。正在进行的实验室研究为放射增敏的基本机制提供了进一步的见解。然而，许多问题仍然没有答案。我们将回顾表明肿瘤快速增殖的数据，S期特异性药物的实验研究以及临床试验的结果。我们还将考虑未来试验的可能设计，基于我们目前对肿瘤增殖和S期特异性药物放射增敏机制的理解。
Clinical and laboratory evidence suggests that several common human cancers contain populations of rapidly proliferating clonogens that may have a substantial impact on local control following conventional radiotherapy. Strategies to improve locoregional control include the use of S-phase-specific radiosensitizers, such as the halogenated pyrimidine analogues (5-iododeoxyuridine, 5-bromodeoxyuridine, fluorodeoxyuridine, 5-fluorouracil) and hydroxyurea. These drugs are taken up and metabolized only by cells synthesizing DNA so that increased tumor proliferation should result in increased radiosensitization. Although the initial clinical trials with these agents were inconclusive, several recent reports have rekindled interest in these radiosensitizers. Ongoing laboratory research has provided further insight into the basic mechanisms of radiosensitization. However, many questions remain unanswered. We will review the data that suggest rapid tumor proliferation, experimental studies with the S-phase-specific drugs, and the results of clinical trials. We will also consider the possible design of future trials based on our current understanding of tumor proliferation and the mechanisms of radiosensitization of S-phase-specific agents.
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