Molecular mechanisms of drug resistance in tyrosine kinases cAbl and cKit.
Crit Rev Biochem Mol Biol
; 46(4): 295-309, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21539479
ABSTRACT
The inhibition of protein kinases has gained general acceptance as an effective approach to treat a wide range of cancers. However, in many cases, prolonged administration of kinase inhibitors often leads to acquired resistance, and the therapeutic effect is subsequently diminished. The wealth of recent studies using biochemical, kinetic, and structural approaches have revealed the molecular basis for the clinically observed resistance. In this review, we highlight several of the most common molecular mechanisms that lead to acquired resistance to kinase inhibitors observed with the cAbl (cellular form of the Abelson leukemia virus tyrosine kinase) and the type III receptor tyrosine kinase cKit, including a newly identified mechanism resulting from accelerated kinase activation caused by mutations in the activation loop. Strategies to overcome the loss of drug sensitivity that represents a challenge currently facing the field and the emerging approaches to circumvent resistance are discussed.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Proteínas de Fusão bcr-abl
/
Proteínas Proto-Oncogênicas c-kit
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Resistencia a Medicamentos Antineoplásicos
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Inibidores de Proteínas Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article