Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma

Faiz Anwer, Kevin Mathew Gee, Ahmad Iftikhar, Mirza Baig, Atlantis Dawn Russ, Sabina Saeed, Muhammad Abu Zar, Faryal Razzaq, Jennifer Carew, Steffan Nawrocki, Hussam Al-Kateb, Nadia Nunes Cavalcante Parr, Ali McBride, Jason Valent, Christy Samaras

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Pages (from-to)397-405
Number of pages9
JournalClinical Lymphoma, Myeloma and Leukemia
Volume19
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • Intracellular pathway
  • MM
  • Mutations
  • Precision medicine
  • Targeted therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Anwer, F., Gee, K. M., Iftikhar, A., Baig, M., Russ, A. D., Saeed, S., Zar, M. A., Razzaq, F., Carew, J., Nawrocki, S., Al-Kateb, H., Cavalcante Parr, N. N., McBride, A., Valent, J., & Samaras, C. (2019). Future of Personalized Therapy Targeting Aberrant Signaling Pathways in Multiple Myeloma. Clinical Lymphoma, Myeloma and Leukemia, 19(7), 397-405. https://doi.org/10.1016/j.clml.2019.03.017