Alexandrova S S, Gladilina Y A, Pokrovskaya M V, Sokolov N N, Zhdanov D D
Institute of Biomedical Chemistry, Moscow, Russia.
Biomed Khim. 2022 Apr;68(2):104-116. doi: 10.18097/PBMC20226802104.
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.
天冬酰胺酶是治疗急性淋巴细胞白血病(最常见的血癌形式)最重要的化疗药物之一。迄今为止,血液学中使用的来自大肠杆菌和达旦氏菌(以前称为菊欧文氏菌)的两种天冬酰胺酶都会诱导癌细胞产生化学抗性,并引发免疫反应超敏形式的副作用。白血病细胞可能由于天冬酰胺合成酶活性增加以及与天冬酰胺酶抗性相关的其他机制而对天冬酰胺酶产生抗性。因此,寻找具有改善药理特性的L-天冬酰胺酶新来源仍然是一项有前景且前瞻性的研究。本文讨论了对L-天冬酰胺酶产生抗性和耐药性的机制,以及克服这些机制的可能方法。