Conventional chemotherapies have showed their limits, notably for patients with advanced cancer. New therapeutic strategies must be identified, and the metabolic abnormalities of cancer cells offer such opportunities. Many human cancer cell lines and primary tumors have absolute requirements for methionine, an essential amino acid. In contrast, normal cells are relatively resistant to exogenous methionine restriction. The biochemical mechanism for methionine dependency has been studied extensively, but the fundamental mechanism remains unclear. A number of investigators have attempted to exploit the methionine dependence of tumors for therapeutic effects in vivo. To reduce in vivo methionine in plasma and tumours, dietary and pharmacological treatments have been used. Methionine-free diet or methionine-deprived total parenteral nutrition causes regression of a variety of animal tumours. Alternatively, methionine depletion was achieved by the use of methioninase. This enzyme specifically degrades methionine and inhibits tumour growth in preclinical models. Because of potential toxicity and quality of life problems, prolonged methionine restriction with diet or with methioninase is not suitable for clinical use. Methionine restriction may find greater application in association with various chemotherapeutic agents. Several preclinical studies have demonstrated synergy between methionine restriction and various cytotoxic chemotherapy drugs. The experimental results accumulated during the last three decades suggest that methionine restriction can become an additional cancer therapeutic strategy, notably in association with chemotherapy.

中文翻译：

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蛋氨酸依赖性和癌症治疗。

常规化学疗法已显示出其局限性，特别是对于晚期癌症患者。必须确定新的治疗策略，癌细胞的代谢异常提供了这样的机会。许多人类癌细胞系和原发性肿瘤对蛋氨酸（一种必需氨基酸）具有绝对的要求。相反，正常细胞对外源蛋氨酸的限制相对抗性。蛋氨酸依赖性的生化机制已被广泛研究，但基本机制仍不清楚。许多研究者已经尝试利用肿瘤的蛋氨酸依赖性来在体内产生治疗效果。为了减少血浆和肿瘤中的体内蛋氨酸，已经使用饮食和药物治疗。不含蛋氨酸的饮食或缺乏蛋氨酸的肠胃外营养会导致多种动物肿瘤消退。或者，通过使用蛋氨酸酶来实现蛋氨酸的消耗。该酶在临床前模型中特异性降解蛋氨酸并抑制肿瘤生长。由于潜在的毒性和生活质量问题，饮食或蛋氨酸酶长时间限制蛋氨酸不适合临床使用。蛋氨酸限制可能会与各种化学治疗剂结合起来发现更多的应用。几项临床前研究已证明蛋氨酸限制与多种细胞毒性化学治疗药物之间具有协同作用。在过去的三十年中积累的实验结果表明，限制蛋氨酸可以成为一种额外的癌症治疗策略，