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Review
. 2022 Apr;68(2):104-116.
doi: 10.18097/PBMC20226802104.

[Mechanisms of development of side effects and drug resistance to asparaginase and ways to overcome them]

[Article in Russian]
S S Alexandrova  1 , Y A Gladilina  1 , M V Pokrovskaya  1 , N N Sokolov  1 , D D Zhdanov  1
Affiliations
Review

[Mechanisms of development of side effects and drug resistance to asparaginase and ways to overcome them]

[Article in Russian]
S S Alexandrova et al. Biomed Khim. 2022 Apr.

Abstract
in English, Russian

Asparaginase is one of the most important chemotherapeutic agents against acute lymphoblastic leukemia, the most common form of blood cancer. To date, both asparaginases from E. coli and Dickeya dadantii (formerly known as Erwinia chrysanthemi), used in hematology, induce chemoresistance in cancer cells and side effects in the form of hypersensitivity of immune reactions. Leukemic cells may be resistant to asparaginase due to the increased activity of asparagine synthetase and other mechanisms associated with resistance to asparaginase. Therefore, the search for new sources of L-asparaginases with improved pharmacological properties remains a promising and prospective study. This article discusses the mechanisms of development of resistance and drug resistance to L-asparaginase, as well as possible ways to overcome them.

Asparaginaza iavliaetsia odnim iz vazhneĭshikh khimioterapevticheskikh sredstv protiv ostrogo limfoblastnogo leĭkoza — naibolee rasprostranennoĭ formy raka krovi. Na segodniashniĭ den' obe ispol'zuemye v gematologii asparaginazy iz Escherichia coli i Dickeya dadantii (ranee izvestnaia kak Erwinia chrysanthemi) indutsiruiut khimiorezistentnost' u rakovykh kletok i pobochnye éffekty v vide giperchuvstvitel'nosti immunnykh reaktsiĭ. Leĭkoznye kletki mogut byt' ne vospriimchivymi k asparaginaze iz-za povyshennoĭ aktivnosti asparaginsintetazy i drugikh mekhanizmov, sviazannykh s ustoĭchivost'iu k asparaginaze. Poétomu poisk novykh produtsentov L-asparaginaz s uluchshennymi farmakologicheskimi svoĭstvami ostaetsia perspektivnym i aktual'nym napravleniem. V dannoĭ rabote rassmotreny mekhanizmy razvitiia rezistentnosti i lekarstvennoĭ ustoĭchivosti k L-asparaginaze, a takzhe vozmozhnye puti ikh preodoleniia.

Keywords: L-asparaginase; antitumor enzymes; drug resistance; immunogenicity.

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