The discovery and development of sorafenib for the treatment of thyroid cancer.
Expert Opin Drug Discov
; 10(4): 427-39, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25662396
INTRODUCTION: Although the prognosis for most differentiated thyroid cancers (DTCs) remains excellent, recurrence and insensitivity to radioactive iodine (RAI) lead to therapeutic challenges and poorer outcomes. In defining the pathogenesis of DTC, multiple genetic alterations have been identified in key pathways focused around receptor tyrosine kinases (RTKs) and the MAPK cascade. Sorafenib was specifically developed to target rapidly accelerated fibrosarcoma (RAF) kinase in the MAPK pathway. It has been shown, however, to have potent inhibition of several key RTKs, RAF kinase and the V600E BRAF mutation, gaining FDA approval in November 2013 for advanced RAI-refractory DTC. AREAS COVERED: The authors provide a review of the targeted RAF kinase discovery strategy as well as the preclinical and clinical development of sorafenib, leading to FDA approval of DTC. The authors also provide some insight into the clinical use of sorafenib and look at important considerations for treatment. EXPERT OPINION: Sorafenib significantly improves progression-free survival in metastatic DTC patients who are RAI-refractory. However, the overall survival benefit is still unproven and requires additional follow up. Despite its cost and significant side-effect profile, which results in dose reductions in the majority of DTC patients, sorafenib should be considered for the treatment of RAI-refractory advanced DTC patients following evaluation of their individual risk-benefit stratification.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
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Neoplasias de la Tiroides
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Niacinamida
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Discov
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido