RESUMO
Trametinib, a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated great promise in treating metastatic melanoma associated with BRAF V600E and V600K mutations; however, it also is highly associated with cutaneous adverse events (AEs). As both BRAF and MEK inhibitors become increasingly used to treat malignant melanoma, it is important to better characterize these AEs so that we can manage them. Herein, we present a case of a 66-year-old man who developed erythematous scaly papules on the face and bilateral upper extremities after beginning therapy with trametinib. The severity of the reaction worsened on trametinib monotherapy compared to combination therapy with a BRAF inhibitor. Biopsy revealed a xanthogranulomatous reaction.
Assuntos
Acrilonitrila/análogos & derivados , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Granuloma/diagnóstico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Xantomatose/diagnóstico , Acrilonitrila/administração & dosagem , Acrilonitrila/efeitos adversos , Acrilonitrila/uso terapêutico , Idoso , Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Diagnóstico Diferencial , Granuloma/induzido quimicamente , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/secundário , Estadiamento de Neoplasias , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Xantomatose/induzido quimicamenteRESUMO
In contrast to extensive studies on familial breast cancer, it is currently unclear whether defects in DNA double strand break (DSB) repair genes play a role in sporadic breast cancer development and progression. We performed analysis of immunohistochemistry in an independent cohort of 235 were sporadic breast tumours. This analysis suggested that RAD51 expression is increased during breast cancer progression and metastasis and an oncogenic role for RAD51 when deregulated. Subsequent knockdown of RAD51 repressed cancer cell migration in vitro and reduced primary tumor growth in a syngeneic mouse model in vivo. Loss of RAD51 also inhibited associated metastasis not only in syngeneic mice but human xenografts and changed the metastatic gene expression profile of cancer cells, consistent with inhibition of distant metastasis. This demonstrates for the first time a new function of RAD51 that may underlie the proclivity of patients with RAD51 overexpression to develop distant metastasis. RAD51 is a potential biomarker and attractive drug target for metastatic triple negative breast cancer, with the capability to extend the survival of patients, which is less than 6 months.