Blokhin Cancer Research Center, Moscow, Russian Federation.
Orekhovich Institute of Biomedical Chemistry, Moscow, Russian Federation.
Curr Med Chem. 2019;26(3):446-464. doi: 10.2174/0929867324666171006132729.
Amino acids are essential components in various biochemical pathways. The deprivation of certain amino acids is an antimetabolite strategy for the treatment of amino acid-dependent cancers which exploits the compromised metabolism of malignant cells. Several studies have focused on the development and preclinical and clinical evaluation of amino acid degrading enzymes, namely L-asparaginase, L-methionine γ-lyase, L-arginine deiminase, L-lysine α-oxidase. Further research into cancer cell metabolism may therefore define possible targets for controlling tumor growth.
The purpose of this review was to summarize recent progress in the relationship between amino acids metabolism and cancer therapy, with a particular focus on Lasparagine, L-methionine, L-arginine and L-lysine degrading enzymes and their formulations, which have been successfully used in the treatment of several types of cancer.
We carried out a structured search among literature regarding to amino acid degrading enzymes. The main aspects of search were in vitro and in vivo studies, clinical trials concerning application of these enzymes in oncology.
Most published research are on the subject of L-asparaginase properties and it's use for cancer treatment. L-arginine deiminase has shown promising results in a phase II trial in advanced melanoma and hepatocellular carcinoma. Other enzymes, in particular Lmethionine γ-lyase and L-lysine α-oxidase, were effective in vitro and in vivo.
The findings of this review revealed that therapy based on amino acid depletion may have the potential application for cancer treatment but further clinical investigations are required to provide the efficacy and safety of these agents.
氨基酸是各种生化途径的必需成分。某些氨基酸的剥夺是治疗依赖氨基酸的癌症的抗代谢策略，利用恶性细胞受损的代谢。几项研究集中在氨基酸降解酶的开发以及临床前和临床评估上，即 L-天冬酰胺酶、L-蛋氨酸 γ-裂解酶、L-精氨酸脱氨酶、L-赖氨酸 α-氧化酶。因此，对癌细胞代谢的进一步研究可能会确定控制肿瘤生长的可能靶点。
本综述的目的是总结氨基酸代谢与癌症治疗之间的最新进展，特别关注 L-天冬酰胺、L-蛋氨酸、L-精氨酸和 L-赖氨酸降解酶及其制剂，这些制剂已成功用于治疗几种类型的癌症。
我们在文献中进行了有关氨基酸降解酶的结构化搜索。搜索的主要方面是体外和体内研究、这些酶在肿瘤学中的应用的临床试验。
大多数已发表的研究都是关于 L-天冬酰胺酶特性及其在癌症治疗中的应用。L-精氨酸脱氨酶在晚期黑色素瘤和肝细胞癌的 II 期试验中显示出有希望的结果。其他酶，特别是 L-蛋氨酸 γ-裂解酶和 L-赖氨酸 α-氧化酶，在体外和体内都有效。
本综述的研究结果表明，基于氨基酸消耗的治疗可能具有癌症治疗的潜在应用，但需要进一步的临床研究提供这些药物的疗效和安全性。
