Article information
Abstract
A number of molecular alterations have been described for melanoma. Melanomas with BRAF mutations tend to be located in areas of intermittent sun exposure, whereas melanomas with KIT mutations mostly appear in acral areas, the mucosa, and areas of chronic sun exposure. Sorafenib, a BRAF inhibitor, has a cytostatic effect on most melanomas with mutations affecting the mitogen-activated protein kinase (MAPK) pathway, and is also capable of triggering apoptosis in a small subgroup of these melanomas. By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. For therapy to be effective, agents should be selected according to the pathways associated with the genetic mutations present in the melanoma.
Keywords:
Melanoma
MAPK
BRAF
KIT
Sorafenib
Imatinib
Resumen
Se han descrito diversas alteraciones moleculares en el melanoma. Los melanomas con mutaciones de BRAF suelen localizarse en zonas con exposición solar intermitente mientras que las alteraciones genéticas de KIT ocurren con mayor frecuencia en los melanomas acrales, mucosos y en los que se localizan en áreas con exposición solar crónica. Sorafenib, un inhibidor de BRAF, tiene un efecto citostático en la mayoría de los melanomas con mutaciones en la vía MAP cinasa, aunque en un pequeño subgrupo de estos melanomas es también capaz de promover la apoptosis. Imatinib, a través de la inhibición de KIT, posee un efecto citostático y citotóxico en aquellos melanomas con mutaciones de KIT, y probablemente en otro subgrupo de melanomas con otras alteraciones genéticas de KIT aún no perfectamente definidas. Para que estos tratamientos sean efectivos es imprescindible que se hayan seleccionado adecuadamente los pacientes, estableciéndose la existencia de alteraciones genéticas en la vía sobre la que se va a actuar.
Palabras clave:
Melanoma
MAPK
BRAF
KIT
Sorafenib
Imatinib
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