Arginine-depleting Enzymes, A Potential Treatment Option for Tumors With Arginine Auxotrophy : A Review

Nurhanis Syafiqah Mohd Nor Hamin, Kok Chang Lee, Wen Nee Tan, Woei Yenn Tong, Chean Ring Leong
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Abstract

The World Health Organization reports that one of the top global causes of illness and mortality is cancer, with nearly 10 million deaths in 2020. Changes in cellular metabolism are common characteristics of a wide variety of malignancies. Enzymatic deficits cause many tumors to lose the ability to synthesize amino acids required for their growth, survival, or proliferation. Thus, some tumors depend on the extra-cellular supply of specific amino acids to meet their needs, allowing them to survive. Amino acid depletion as a targeted therapy takes advantage of these tumor traits by depleting certain amino acids in the body that is required for the tumor to survive. This review aims to discuss the potential and challenges of arginine-depleting enzymes as a means in treating arginine auxotrophic cancers. Previously, arginine deiminase (ADI) of bacterial origin has been studied for the in vivo arginine auxotrophic tumour therapy. However, it has been hampered by drawbacks, including immunogenicity and toxicity issues. Thus, human arginase I (hARGI) has been considered a better candidate due to its low mmunogenicity and toxicity effects. However, hARGI’s application as an anti-cancer drug is hindered by its low activity towards arginine owing to its high Km values indicating the enzyme’s low substrate affinity. Thus, it is necessary to improve the enzyme catalytic capability and stability for more practical application in therapeutic cancer treatment. With the advancement of bioinformatics tools, more studies are anticipated to rationally engineer the enzyme for more practical clinical application in the treatment of arginine auxotrophic cancers.
精氨酸消耗酶:精氨酸营养不良肿瘤的潜在治疗选择
世界卫生组织报告称,全球最主要的疾病和死亡原因之一是癌症,2020年将有近1000万人死亡。细胞代谢的改变是多种恶性肿瘤的共同特征。酶缺陷导致许多肿瘤失去合成其生长、存活或增殖所需氨基酸的能力。因此,一些肿瘤依靠细胞外特定氨基酸的供应来满足它们的需要,使它们能够生存。氨基酸消耗作为一种靶向治疗,通过消耗体内肿瘤生存所需的某些氨基酸,利用了肿瘤的这些特征。本综述旨在讨论精氨酸消耗酶作为治疗精氨酸营养不良癌症的一种手段的潜力和挑战。以前,细菌来源的精氨酸脱亚胺酶(ADI)已被研究用于体内精氨酸营养不良肿瘤的治疗。然而,它一直受到缺陷的阻碍,包括免疫原性和毒性问题。因此,由于其低免疫原性和毒性作用,人精氨酸酶I (hARGI)被认为是一个更好的候选者。然而,hARGI作为抗癌药物的应用受到阻碍,因为它对精氨酸的活性较低,因为它的高Km值表明该酶对底物的亲和力较低。因此,有必要提高酶的催化能力和稳定性,以便在治疗性癌症方面有更多的实际应用。随着生物信息学工具的进步,期望更多的研究能够合理地设计酶,使其在精氨酸营养不良癌症的治疗中得到更实际的临床应用。
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来源期刊
CiteScore
0.50
自引率
0.00%
发文量
28
期刊介绍: The Malaysian Journal of Medicine and Health Sciences (MJMHS) is published by the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. The main aim of the MJMHS is to be a premier journal on all aspects of medicine and health sciences in Malaysia and internationally. The focus of the MJMHS will be on results of original scientific research and development, emerging issues and policy analyses pertaining to medical, biomedical and clinical sciences.
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