Signaling pathways modulating dependence of lung cancer on mutant epidermal growth factor receptor and mechanisms of intrinsic and acquired resistance to tyrosine kinase inhibitors.
Curr Pharm Des
; 20(24): 3883-93, 2014.
Article
en En
| MEDLINE
| ID: mdl-24138718
ABSTRACT
A new era in lung cancer targeted therapy arrived with the discovery of a subset of lung adenocarcinomas harboring activating mutations of the epidermal growth factor receptor (EGFR), whose tyrosine kinase activity can be selectively blocked by small molecule pharmaceuticals referred as tyrosine kinase inhibitors (TKIs). This was the starting point for a less toxic and more effective treatment strategy for a disease that has historically presented as chemorefractory and highly lethal. In spite of this progress, only 80% of the patients treated with this class of compounds will obtain a clinical benefit, of variable magnitude and duration, with remaining patients being primarily refractory to the treatment. Moreover, responding tumors will eventually develop acquired resistance to TKIs and progress to more advanced stages. In this review we summarize the current knowledge with regard to the mechanisms leading to tumor regression and the modifiers of this primary response that determine significant variability in sensitivity of tumors harboring EGFR activating mutations, ranging from complete remission to primary refractoriness. We also analyze the mechanisms of secondary resistance and the strategies the scientific community is exploring in order to overcome these barriers.
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Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Inhibidores de Proteínas Quinasas
/
Receptores ErbB
/
Neoplasias Pulmonares
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Pharm Des
Asunto de la revista:
FARMACIA
Año:
2014
Tipo del documento:
Article