Predictive markers for efficiency of the amino-acid deprivation therapies in cancer

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.

Authors
Pokrovsky Vadim S. 1, 2, 3 , Abo Qoura Louay 1 , Morozova Elena4 , Bunik Victoria I.5, 6, 7
Publisher
Frontiers Media S.A.
Language
English
Status
Published
Volume
9
Year
2022
Organizations
  • 1 Laboratory of Experimental Oncology, Research Institute of Molecular and Cellular Medicine, People’s Friendship University of Russia (RUDN University)
  • 2 Laboratory of Combined Treatment, N.N. Blokhin National Medical Research Center of Oncology of Ministry of Health of Russian Federation
  • 3 Department of Biotechnology, Sirius University of Science and Technology
  • 4 Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
  • 5 A.N. Belozersky Institute of Physicochemical Biology, M.V. Lomonosov Moscow State University
  • 6 Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University
  • 7 Department of Biological Chemistry, Sechenov First Moscow State Medical University
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