The potential of methioninase for cancer treatment.
Biochim Biophys Acta Rev Cancer
; 1879(4): 189122, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38796027
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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MEDLINE
Assunto principal:
Liases de Carbono-Enxofre
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Neoplasias
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En
Ano de publicação:
2024
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Article