Bagshawe K D
Lancet. 1986 Oct 4;2(8510):778-81. doi: 10.1016/s0140-6736(86)90301-6.
Chemotherapeutic agents that have come into clinical use because of their selective effect against cancers have limited success mainly because many cancer cells become resistant to them. Some chemotherapeutic agents inhibit DNA synthesis in normal cells but not in tumour cells so that nucleoside analogues with cell-killing potential can be incorporated into cancer cells when they continue to synthesise DNA in the presence of agents that stop DNA synthesis in normal cells. The potential of halogenated pyrimidines as sensitisers of cancers to ionising and photo-irradiation might be extended by giving them with agents that inhibit their uptake by normal tissues. A similar approach might also be used with conventional cytotoxic chemotherapy. Radiolabelled pyrimidine analogues may have a role in treating tumours resistant to inhibitors of DNA synthesis. They may also prove useful agents for gamma-camera imaging when normal tissue uptake is blocked.
由于对癌症具有选择性作用而进入临床应用的化疗药物取得的成功有限，主要是因为许多癌细胞对它们产生了抗性。一些化疗药物抑制正常细胞中的DNA合成，但不抑制肿瘤细胞中的DNA合成，因此当癌细胞在能阻止正常细胞DNA合成的药物存在时继续合成DNA时，具有细胞杀伤潜力的核苷类似物就可以掺入癌细胞中。通过将卤代嘧啶与抑制其被正常组织摄取的药物联合使用，可能会扩大其作为癌症对电离辐射和光辐射敏化剂的潜力。类似的方法也可用于传统的细胞毒性化疗。放射性标记的嘧啶类似物可能在治疗对DNA合成抑制剂耐药的肿瘤中发挥作用。当正常组织摄取被阻断时，它们也可能被证明是用于伽马相机成像的有用药物。
