The potential of methioninase for cancer treatment

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-05-23 DOI:10.1016/j.bbcan.2024.189122
Louay Abo Qoura , Konstantin V. Balakin , Robert M. Hoffman , Vadim S. Pokrovsky
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Abstract

Cancer cells are addicted to L-methionine (L-Met) and have a much greater requirement for L-Met than normal cells due to excess transmethylation, termed the Hoffman effect. By targeting this vulnerability through dietary restriction of L-Met, researchers have been able to achieve promising results in inhibiting tumor growth and eradicating cancer cells. Methioninase (EC 4.4.1.11; METase) catalyzes the transformation of L-Met into α-ketobutyrate, ammonia, and methanethiol. The use of METase was initially limited due to its poor stability in vivo, high immunogenicity, and enzyme-induced inactivating antibodies. These issues could be partially resolved by PEGylation, encapsulation in erythrocytes, and various site-directed mutagenesis. The big breakthrough came when it was discovered that METase is effectively administered orally. The enzyme L-asparaginase is approved by the FDA for treatment of acute lymphoblastic leukemia. METase has more potential as a therapeutic since addiction to L-Met is a general and fundamental hallmark of cancer.

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蛋氨酸酶治疗癌症的潜力
癌细胞对 L-蛋氨酸(L-Met)上瘾,由于过量的跨甲基化(即霍夫曼效应),癌细胞对 L-Met 的需求比正常细胞大得多。针对这一弱点,研究人员通过限制饮食中的 L-Met,在抑制肿瘤生长和消灭癌细胞方面取得了可喜的成果。甲硫氨酸酶(EC 4.4.1.11;METase)催化 L-Met 转化为 α-酮丁酸、氨和甲硫醇。由于 METase 在体内稳定性差、免疫原性高以及酶诱导的失活抗体,它的使用最初受到限制。这些问题可以通过聚乙二醇化、封装在红细胞中以及各种定点诱变得到部分解决。当人们发现 METase 可以有效地口服给药时,取得了重大突破。L-天冬酰胺酶已被美国食品及药物管理局批准用于治疗急性淋巴细胞白血病。METase 更有可能成为一种疗法,因为对 L-Met 上瘾是癌症的普遍和基本特征。
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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