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Information × Registration Number 0225U005362, (0122U002256) , R & D reports Title Development of new selective approaches to metabolic antitumor therapy based on recombinant human arginase and cellular stress modulators popup.stage_title Аналіз впливу рекомбінантної аргінази-І у комбінації з дефіцитом інших амінокислот (та/чи інгібіторів метаболізму окремих амінокислот) на життєздатність, міграцію, та клоногенний потенціал пухлинних клітин Head Stasyk Oleh V., Доктор біологічних наук Registration Date 30-12-2025 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description1 The aim of this work is to develop and analyze new combined approaches to antitumor metabolic therapy based on recombinant human arginase and cellular stress inducers, including analogues of arginine (canavanine, indospicin), analogues of pyrimidine bases, and energy metabolism modulators. Also, the work's goal is the identification of new molecular markers of human tumor cell sensitivity to appropriate therapy to develop more effective and selective approaches and predict the effectiveness of their application to different types of tumors popup.description2 Research report, stage 4: 43 p., 15 fig., 2 tables. The Department of Cell Signaling conducted research aimed at developing new approaches to metabolic cancer therapy based on starvation of arginine and other amino acids. It was shown for the first time that combined metabolic therapy based on recombinant human arginase and the arginine analogue canavanine leads to effective inhibition of transcription of the arginine anabolism gene argininosuccinate synthetase (ASS1) and the asparagine biosynthesis gene asparagine synthetase (ASNS). Thus, for certain types of tumors, double starvation of the amino acids arginine and asparagine (or glutamine, taking into account the concomitant glutaminase activity of some recombinant asparaginases) and one of the arginine analogs of plant origin (canavanine, indospicin) can be used to avoid the emergence of therapy-resistant clones with a restored ability to resynthesize the corresponding amino acids. It was shown that the corresponding transcriptional inhibition mechanism for ASS1 is independent of the HIF1Alpha-c-MYC signaling pathway and is induced only by proteinogenic arginine analogs, thus indicating a probable GCN2-eIF2a-dependent mechanism of regulation. In models of prostate carcinomas and head and neck cancer, the possibility of creating combined arginine and glutamine starvation using recombinant hydrolases of the corresponding amino acids and/or low-molecular inhibitors was demonstrated. According to the results of the research, during 2025, 3 scientific articles were published, included in the international scientometric databases Web of Science and Scopus in foreign scientific publications with a total IF of 11.2 (Q1), 1 chapter of a monograph in a foreign publishing house and 9 abstracts of reports at international conferences; 1 patent of Ukraine for a utility model was also obtained. Keywords: human tumor cells, recombinant human arginase, asparaginase, inhibitors of amino acid metabolism Product Description popup.authors Dmytro V. Demash Olena I. Vovk Воробець Зіновій Дмитрович Halyna Y. Shuvaieva Svitlana V. Chernyshuk Stasyk Olena H. Nikita V. Polishchuk popup.nrat_date 2025-12-30 Close