Recombinant arginine‐degrading enzymes in metabolic anticancer therapy and bioanalytics

Abstract

Tumor cells often exhibit specific metabolic defects due to the aberrations in oncogene-dependent regulatory and/or signaling pathways that distinguish them from normal cells. Among others, many malignant cells are deficient in biosynthesis of certain amino acids and concomitantly exhibit elevated sensitivity to deprivation of these amino acids. Although the underlying causes of such metabolic changes are still not fully understood, this feature of malignant cells is exploited in metabolic enzymotherapies based on single amino acid, e.g., arginine, deprivation. To achieve efficient arginine depletion in vivo, two recombinant enzymes, bacterial arginine deiminase and human arginase I have been evaluated and are undergoing further development. This review is aimed to summarize the current knowledge on the application of arginine-degrading enzymes as anticancer agents and as bioanalytical tools for arginine assays. The problems that have to be solved to optimize this therapy for clinical application are discussed.

Metallic Nanoparticles Obtained via “Green” Synthesis as a Platform for Biosensor Construction

“…The recombinant yeast strain O. polymorpha NCYC495-pGAP1-HsARG1 (leu2car1 Sc:LEU2) [59] was used as a tool for the green synthesis of gNPs. The cells were cultivated in Erlenmeyer flasks under aeration in a circular shaker (200 rpm) at 30 • C, for 48 h as described earlier [56].…”

Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma

“…1. Furthermore, arginine deprivation and inhibition of urea cycle and arginine biosynthesis have been suggested as potential cancer treatment strategies [55,56]. The RNA sequence data were used to build patient-specific metabolic models (1A).…”

Arginine Deprivation Therapy: Putative Strategy to Eradicate Glioblastoma Cells by Radiosensitization

“…This is particularly striking for malignancies deficient in one key enzyme of arginine synthesis due to genetic or epigenetic modifications. In most cases, except for hepatocellular carcinoma, the enzyme ASS is lacking in these arginine auxotrophic tumors, and enzymotherapeutic arginine deprivation therapy (ADT) has already proven to effectively inhibit growth of such cancers in preclinical studies and clinical phase I-III trials (1,(4)(5)(6)(7)(8). ADT combined with radiotherapy is not yet in clinical trial.…”

“…It is thus independent of the blood-brain barrier, which, in spite of its partially enhanced permeability in brain cancer patients (11,12), often impairs adequate drug distribution. The translation of the initial finding that arginine withdrawal induces growth arrest in various tumor entities in vitro via ADT-based animal studies into clinical trials has just commenced and progresses rapidly (1,6,8,9,(13)(14)(15)).…”