KRAS/NRAS/BRAF Mutations as Potential Targets in Multiple Myeloma.

BRAF KRAS NRAS multiple myeloma therapeutics

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2019
Historique:
received: 25 07 2019
accepted: 10 10 2019
entrez: 12 11 2019
pubmed: 12 11 2019
medline: 12 11 2019
Statut: epublish

Résumé

In multiple myeloma the mutational profile is mainly represented by translocations involving chromosome 14 and by single nucleotide mutations, frequently involving genes implicated in the mitogen activated protein kinase (MAPK) pathway, as KRAS, NRAS, and, less frequently, BRAF. Because KRAS/NRAS/BRAF mutations are associated with a higher number of mutations per patient, we hypothesize that this group of patients could benefit from therapy with checkpoint inhibitors because of the higher frequency of neo-antigens that this group would present. This might also true for IMiD therapy, because of their activatory effect on T cells. Because, KRAS/NRAS/BRAF are members of the MAPK pathway, this subgroup of patients would also benefit from inhibitors of MAPK, either directly on the specific mutation or through downstream targeting of MEK1/2 or ERK1/2 to account for a possible compensatory collateral signaling that might activate as response to upstream inhibition.

Identifiants

pubmed: 31709194
doi: 10.3389/fonc.2019.01137
pmc: PMC6821642
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1137

Informations de copyright

Copyright © 2019 Pasca, Tomuleasa, Teodorescu, Ghiaur, Dima, Moisoiu, Berce, Stefan, Ciechanover and Einsele.

Références

Oncotarget. 2016 Apr 26;7(17):23312-21
pubmed: 27004405
Blood. 2015 Jul 16;126(3):300-10
pubmed: 26031917
Blood. 2014 Jan 30;123(5):632-9
pubmed: 24335104
Front Immunol. 2018 Nov 16;9:2431
pubmed: 30505301
Oncotarget. 2015 Sep 15;6(27):24205-17
pubmed: 26090869
Nat Rev Dis Primers. 2017 Jul 20;3:17046
pubmed: 28726797
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Cancer Cell. 2014 Jan 13;25(1):91-101
pubmed: 24434212
Front Immunol. 2018 Sep 26;9:2204
pubmed: 30319648
Acta Pharm Sin B. 2018 Jul;8(4):552-562
pubmed: 30109180
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Curr Cancer Drug Targets. 2017;17(9):846-857
pubmed: 28201976

Auteurs

Sergiu Pasca (S)

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Ciprian Tomuleasa (C)

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania.
Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Patric Teodorescu (P)

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania.

Gabriel Ghiaur (G)

Department of Leukemia, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States.

Delia Dima (D)

Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania.

Vlad Moisoiu (V)

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Cristian Berce (C)

Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Cristina Stefan (C)

African Organisation for Research and Training in Cancer, Cape Town, South Africa.

Aaron Ciechanover (A)

The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.

Herman Einsele (H)

Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany.

Classifications MeSH