RESUMO
Most uveal melanomas harbor mutations in Gαq and show constitutive MAPK activation. Although MEK inhibition has some efficacy against uveal melanoma, clinical responses are typically poor. The Gαq inhibitor-MEK inhibitor combination showed prolonged suppression of MAPK signaling in preclinical uveal melanoma models and led to improved therapeutic responses.See related article by Hitchman et al., p. 1476.
Assuntos
Melanoma , Neoplasias Uveais , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/genéticaRESUMO
Different animal models have been proposed to investigate the mechanisms of Human T-lymphotropic Virus (HTLV)-induced pathogenesis: rats, transgenic and NOD-SCID/γcnull (NOG) mice, rabbits, squirrel monkeys, baboons and macaques. These systems indeed provide useful information but have intrinsic limitations such as lack of disease relevance, species specificity or inadequate immune response. Another strategy based on a comparative virology approach is to characterize a related pathogen and to speculate on possible shared mechanisms. In this perspective, bovine leukemia virus (BLV), another member of the deltaretrovirus genus, is evolutionary related to HTLV-1. BLV induces lymphoproliferative disorders in ruminants providing useful information on the mechanisms of viral persistence, genetic determinants of pathogenesis and potential novel therapies.
Assuntos
Interações Hospedeiro-Patógeno , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Vírus da Leucemia Bovina/fisiologia , Animais , Pesquisa Biomédica/tendências , Modelos Animais de Doenças , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Humanos , Vírus da Leucemia Bovina/patogenicidade , Virologia/tendênciasRESUMO
Malignant pleural mesothelioma (MPM) is an almost invariably fatal cancer of the pleura due to asbestos exposure. Increasing evidence indicates that unresponsiveness to chemotherapy is due to epigenetic errors leading to inadequate gene expression in tumor cells. The availability of compounds that modulate epigenetic modifications, such as histone acetylation or DNA methylation, offers new prospects for treatment of MPM. Here, we review latest findings on epigenetics in mesothelioma and present novel strategies for promising epigenetic therapies.
