Asunto(s)
Adenina/análogos & derivados , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Leucemia Linfocítica Crónica de Células B/complicaciones , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Piel/patología , Adenina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/etiologíaRESUMEN
We report three cases of skin toxicity associated with oral mitogen-activated protein kinase kinase (MEK) inhibitor treatment for metastatic malignant melanoma (MM). All three patients developed oedema, and a single patient experienced eyelash trichomegaly. This is the first known report of eyelash trichomegaly secondary to MEK inhibitor use. We also discuss possible mechanisms for MEK inhibitor-associated oedema development. This series supports the role of the dermatologist in the screening and management of patients in the rapidly developing oncology setting, as new targeted agents can give rise to marked skin toxicity.
Asunto(s)
Acrilonitrilo/análogos & derivados , Compuestos de Anilina/efectos adversos , Edema/inducido químicamente , Melanoma/tratamiento farmacológico , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/efectos adversos , Enfermedades de la Piel/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Acrilonitrilo/efectos adversos , Adulto , Femenino , Humanos , Masculino , Melanoma/secundario , Persona de Mediana Edad , Neoplasias Cutáneas/secundarioRESUMEN
Defects in the NF1 gene have been implicated in the inherited disorder neurofibromatosis type 1, which is characterized by several developmental abnormalities including an increased frequency of benign and malignant tumours of neural crest origin (neurofibromas and neurofibrosarcomas respectively). The NF1 gene encodes a ubiquitous protein homologous to p120GAP, the GTPase-activating protein (GAP) for the products of the ras protooncogenes. When expressed in non-mammalian systems, the region of the NF1 gene homologous to p120GAP produces a protein with GAP-like activity. Here we present evidence that the ras proteins in malignant tumour cell lines from patients with type 1 neurofibromatosis are in a constitutively activated state, as judged by the guanine nucleotide bound to them, and are necessary for cellular proliferation. These cells contain p21ras and p120GAP that are both functionally wild type, but barely any functional NF1 protein. Our results show that the NF1 protein is normally essential for correct negative regulation of ras proteins in the cell, even in the presence of normal p120GAP, and they support the hypothesis that NF1 is a tumour-suppressor gene whose product acts upstream of ras.