Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma.
Intracellular pathway
MM
Mutations
Precision medicine
Targeted therapy
Journal
Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
10
10
2018
revised:
19
02
2019
accepted:
17
03
2019
pubmed:
1
5
2019
medline:
5
8
2020
entrez:
1
5
2019
Statut:
ppublish
Résumé
Multiple myeloma (MM) is a genetically complex disease. Identification of mutations and aberrant signaling pathways that contribute to the progression of MM and drug resistance has potential to lead to specific targets and personalized treatment. Aberrant signal pathways include RAS pathway activation due to RAS or BRAF mutations (targeted by vemurafenib alone or combined with cobimetinib), BCL-2 overexpression in t(11:14) (targeted by venetoclax), JAK2 pathway activation (targeted by ruxolitinib), NF-κB pathway activation (treated with DANFIN combined with bortezomib), MDM2 overexpression, and PI3K/mTOR pathway activation (targeted by BEZ235). Cyclin D1 (CCND1) and MYC are also emerging as key potential targets. In addition, histone deacetylase inhibitors are already in use for the treatment of MM in combination therapy, and targeted inhibition of FGFR3 (AZD4547) is effective in myeloma cells with t(4;14) translocation. Bromodomain and extra terminal (BET) protein antagonists decrease the expression of MYC and have displayed promising antimyeloma activity. A better understanding of the alterations in signaling pathways that promote MM progression will further inform the development of precision therapy for patients.
Identifiants
pubmed: 31036508
pii: S2152-2650(18)31463-0
doi: 10.1016/j.clml.2019.03.017
pmc: PMC6626550
mid: NIHMS1525331
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
397-405Subventions
Organisme : NCI NIH HHS
ID : P30 CA023074
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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