Pharmacological targeting of bet bromodomain proteins in acute myeloid leukemia and malignant lymphomas : From molecular characterization to clinical applications
Reyes-Garau, D. (Hospital Universitari Vall d'Hebron)
Ribeiro, Marcelo L. (Vall d'Hebron Institut de Recerca (VHIR))
Roué, Gaël (Vall d'Hebron Institut de Recerca (VHIR))
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	A25in25proarENG-pr910210011and DNA-protein interactions and abnormal chromatin remodeling are a major cause of uncontrolled gene transcription and constitutive activation of critical signaling pathways in cancer cells. Multiple epigenetic regulators are known to be deregulated in several hematologic neoplasms, by somatic mutation, amplification, or deletion, allowing the identification of specific epigenetic signatures, but at the same time providing new therapeutic opportunities. While these vulnerabilities have been traditionally addressed by hypomethylating agents or histone deacetylase inhibitors, pharmacological targeting of bromodomain-containing proteins has recently emerged as a promising approach in a number of lymphoid and myeloid malignancies. Indeed, preclinical and clinical studies highlight the relevance of targeting the bromodomain and extra-terminal (BET) family as an efficient strategy of target transcription irrespective of the presence of epigenetic mutations. Here we will summarize the main advances achieved in the last decade regarding the preclinical and clinical evaluation of BET bromodomain inhibitors in hematologic cancers, either as monotherapies or in combinations with standard and/or experimental agents. A mention will finally be given to the new concept of the protein degrader, and the perspective it holds for the design of bromodomain-based therapies.
Ayudas:	Instituto de Salud Carlos III PI15-00102 Instituto de Salud Carlos III PI18-01383
Nota:	Altres ajuts: G.R. acknowledges supports from European Regional Development Fund (ERDF) "Una manera de hacer Europa".
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	BRD2 ; BRD4 ; Bromodomain and Extra-Terminal Domain ; MYC ; NF-κB ; Combination therapy ; Hematological malignancies ; Protein degraders ; Super-enhancer
Publicado en:	Cancers, Vol. 11 Núm. 10 (october 2019) , p. 1483, ISSN 2072-6694

DOI: 10.3390/cancers11101483
PMID: 31581671

19 p, 1.1 MB

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