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Hypothesis and Theory ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.01137

KRAS/NRAS/BRAF mutations as potential targets in multiple myeloma

 Sergiu Pasca1,  Ciprian Tomuleasa1*, Gabriel Ghiaur2, Delia Dima3,  Vlad Moisoiu1,  Cristian Berce1, Cristina Stefan4, Aaron Ciechanover5 and Hermann Einsele6
  • 1Iuliu Hațieganu University of Medicine and Pharmacy, Romania
  • 2Johns Hopkins University, United States
  • 3Oncology Institute Prof. Dr. Ion Chiricuta, Romania
  • 4African Organisation for Research and Training in Cancer, South Africa
  • 5Rappaport Family Institute for Research in the Medical Sciences, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Israel
  • 6Universitätsklinikum Würzburg, Germany

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.

Keywords: Multiple Myeloma, KRAS, BRAF, NRAS, Therapeutics

Received: 25 Jul 2019; Accepted: 10 Oct 2019.

Copyright: © 2019 Pasca, Tomuleasa, Ghiaur, Dima, Moisoiu, Berce, Stefan, Ciechanover and Einsele. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ciprian Tomuleasa, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, 400012, Romania, ciprian.tomuleasa@umfcluj.ro