Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors.

Kefford, Richard; Arkenau, Hendrik‐Tobias; Brown, Michael P.; Millward, M. J.; Infante, J. R.; Long, G. V.; Ouellet, Danielle; Curtis, M.; Lebowitz, Peter F.; Falchook, G. S.

doi:10.1200/jco.2010.28.15_suppl.8503

Cited by 253 publications

(212 citation statements)

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“…This clinical finding is consistent with work in preclinical models that demonstrated that treatment of human melanoma cell lines with a wild-type BRAF gene with PLX4720 and other selective BRAF inhibitors resulted in hyperactivation of MEK and MAPK, and increased growth of cancer cells in vitro and in vivo (Halaban et al 2010;Hatzivassiliou et al 2010;Heidorn et al 2010;Poulikakos et al 2010). A second selective inhibitor of the BRAF V600E protein, GSK2118436, has demonstrated similar activity, with a 62% ORR in phase I testing in advanced melanoma patients with a BRAF mutation (Kefford et al 2010). While the high response rate with minimal toxicity with PLX4032 and GSK2118436 is unprecedented, it is now becoming clear that resistance will be a major problem with these agents.…”

Section: The Ras/raf/mapk Pathwaysupporting

confidence: 72%

New Molecular Targets for the Systemic Therapy of Melanoma

Ahmed¹,

Davies²

2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

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Section: The Ras/raf/mapk Pathwaysupporting

confidence: 72%

New Molecular Targets for the Systemic Therapy of Melanoma

Ahmed¹,

Davies²

2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

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“…Within the Rafmitogen-activated protein kinase (MAPK) cascade, potent inhibitors of BRaf, CRaf, and MEK are in clinical use (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Although very encouraging, the clinical responses to Raf inhibitors can be relatively short-lived, with treatment failure and tumor progression occurring due to acquired resistance, primarily as a result of secondary mutations in oncogenic BRaf or other proteins such as N-Ras or MEK (14)(15)(16).…”

mentioning

confidence: 99%

Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission

Hoeven¹,

Cho²,

Ma³

et al. 2013

Molecular and Cellular Biology

109

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“…La mediana de supervivencia fue de 10 meses para los tratados con ipilimumab y 6 para los no tratados, con una supervivencia a dos años del 24% en el brazo del ipilimumab, que se mantenían a lo largo del seguimiento 11 . Otros fármacos con capacidad selectiva de inhibición de la forma mutada de B-RAF (GSK218436/PLX4032) 12,13 , de inhibición de la actividad tirosín-Kinasa de c-KIT (imatinib/sorafenib) 14 , así como de inducción de apoptosis a través de la vía intrínseca (tasisulam) 15 también están mostrando resultados positivos. En el caso presentado no se pudieron determinar marcadores experimentales al no estar previsto en el estudio.…”

Section: Discussionunclassified

Respuesta completa tras tratamiento con bioquimioterapia en un caso de melanoma cutáneo diseminado

Bermejo-Pérez

Villar-Chamorro

Lemos-Simosomo

et al. 2011

Anales Sis San Navarra

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notas clínicas0Respuesta completa tras tratamiento con bioquimioterapia en un caso de melanoma cutáneo diseminado Complete response in a patient with a metastatic cutaneous melanoma M.J. Bermejo-Pérez, E. Villar-chamorro, M. lemos-simosomo, c. García-González, a.M. Galeote-Miguel REsUMEnFundamento. El pronóstico del melanoma diseminado es muy sombrío. Actualmente no hay consenso sobre el tratamiento estándar en primera línea para el melanoma metastático. Se presenta un caso por su comportamiento excepcional.Resultados. Varón de 43 años diagnosticado en 1999 de melanoma maligno estadio IIA. En mayo de 2000 se objetivaron metástasis hepáticas y esplénicas. Recibió 6 ciclos de bioquimioterapia (cisplatino y DTIC junto con interleukina-2 e interferón-α) cada 21 días y otros 6 ciclos con inmunoterapia sola (interleukina-2 e interferón-α). Actualmente el paciente sigue vivo y sin evidencia de enfermedad.conclusión. El melanoma cutáneo metastático, en ocasiones, presenta una inusual evolución favorable. Es de esperar que los métodos de detección de marcadores moleculares logren determinar factores implicados en este tipo de respuesta y que los nuevos tratamientos dirigidos consigan mantener esta tendencia positiva.Palabras clave. Melanoma. Quimioterapia. Inmunoquimioterapia. aBstRactBackground. The management of patients with disseminated disease is a difficult problem. There is currently no consensus on the standard first-line treatment for metastatic melanoma. We present a case because of his exceptional evolution. Results.A 43 year old male diagnosed in 1999 with malignant melanoma stage IIA. In May 2000, hepatic and splenic metastases were detected. He received 6 cycles of biochemotherapy (cisplatin and DTIC, plus interleukin-2 and interferon-α) and another 6 cycles with single immunotherapy (interleukin-2 and interferon-α). Today, the patient is still alive and without evidence of disease.conclusion. Metastatic cutaneous melanoma, sometimes, presents and unusual and favourable evolution. In the near future, the methods of detection of molecular markers are expected to identify factors involved in this type of response. Furthermore, new targeted therapies may become essential to maintain this positive trend.

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Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors.

Cited by 253 publications

References 0 publications

New Molecular Targets for the Systemic Therapy of Melanoma

New Molecular Targets for the Systemic Therapy of Melanoma

Fendiline Inhibits K-Ras Plasma Membrane Localization and Blocks K-Ras Signal Transmission

Respuesta completa tras tratamiento con bioquimioterapia en un caso de melanoma cutáneo diseminado

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