Pokrovsky Vadim S, Abo Qoura Louay, Morozova Elena, Bunik Victoria I
Laboratory of Experimental Oncology, Research Institute of Molecular and Cellular Medicine, People's Friendship University of Russia (RUDN University), Moscow, Russia.
Laboratory of Combined Treatment, N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of Russian Federation, Moscow, Russia.
Front Med (Lausanne). 2022 Nov 3;9:1035356. doi: 10.3389/fmed.2022.1035356. eCollection 2022.
Amino acid deprivation therapy (AADT) is a promising strategy for developing novel anticancer treatments, based on variations in metabolism of healthy and malignant cells. L-asparaginase was the first amino acid-degrading enzyme that received FDA approval for the treatment of acute lymphoblastic leukemia (ALL). Arginase and arginine deiminase were effective in clinical trials for the treatment of metastatic melanomas and hepatocellular carcinomas. Essential dependence of certain cancer cells on methionine explains the anticancer efficacy of methionine-g-lyase. Along with significant progress in identification of metabolic vulnerabilities of cancer cells, new amino acid-cleaving enzymes appear as promising agents for cancer treatment: lysine oxidase, tyrosine phenol-lyase, cysteinase, and phenylalanine ammonia-lyase. However, sensitivity of specific cancer cell types to these enzymes differs. Hence, search for prognostic and predictive markers for AADT and introduction of the markers into clinical practice are of great importance for translational medicine. As specific metabolic pathways in cancer cells are determined by the enzyme expression, some of these enzymes may define the sensitivity to AADT. This review considers the known predictors for efficiency of AADT, emphasizing the importance of knowledge on cancer-specific amino acid significance for such predictions.
基于健康细胞和恶性细胞代谢的差异，氨基酸剥夺疗法（AADT）是开发新型抗癌治疗方法的一种有前景的策略。L-天冬酰胺酶是首个获得美国食品药品监督管理局（FDA）批准用于治疗急性淋巴细胞白血病（ALL）的氨基酸降解酶。精氨酸酶和精氨酸脱亚氨酶在转移性黑色素瘤和肝细胞癌的治疗临床试验中有效。某些癌细胞对蛋氨酸的绝对依赖性解释了蛋氨酸γ-裂解酶的抗癌疗效。随着在识别癌细胞代谢脆弱性方面取得重大进展，新的氨基酸裂解酶成为有前景的癌症治疗药物：赖氨酸氧化酶、酪氨酸酚裂解酶、半胱氨酸酶和苯丙氨酸解氨酶。然而，特定癌细胞类型对这些酶的敏感性不同。因此，寻找AADT的预后和预测标志物并将这些标志物引入临床实践对转化医学至关重要。由于癌细胞中的特定代谢途径由酶表达决定，其中一些酶可能决定对AADT的敏感性。本综述考虑了已知的AADT疗效预测指标，强调了了解癌症特异性氨基酸意义对于此类预测的重要性。
