RESUMO
Erdheim Chester Disease (ECD) is a rare histiocytic disorder marked by infiltration of organs with CD68+ histiocytes. ECD stems from mutations of BRAF and MAP2K1 in hematopoietic stem and progenitor cells (HSPCs), which further differentiate into monocytes and histiocytes. Histopathology reveals lipid-containing histiocytes, which test positive for CD68 and CD133 in immunohistochemistry. Signs and symptoms vary and depend on the organ/s of manifestation. Definitive radiological results associated with ECD include hairy kidney, coated aorta, and cardiac pseudotumor. Treatment options primarily include anti-cytokine therapy and inhibitors of BRAF and MEK signaling.
Assuntos
Doença de Erdheim-Chester , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/diagnóstico , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/terapia , Doença de Erdheim-Chester/patologia , Doença de Erdheim-Chester/metabolismo , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Histiócitos/patologia , Histiócitos/metabolismoRESUMO
Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological setting, it is associated with oncogenesis and is responsible for disease progression and poor clinical outcomes. Hedgehog signaling mediates downstream actions via Glioma Associated Oncogene Homolog (GLI) transcription factors. Inhibiting Hh signaling is an important oncological strategy in which inhibitors of the ligands SMO or GLI have been looked at. This review briefly narrates the Hh ligands, signal transduction, the target genes involved and comprehensively describes the numerous inhibitors that have been evaluated for use in various neoplastic settings.