Future of personalized therapy targeting aberrant signaling pathways in multiple myeloma

Publication date: Available online 25 March 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): 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-Katab, Nadia Nunes Cavalcante, Ali McBride, Jason Valent, Christy SamarasAbstractMultiple myeloma (MM) is 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 vermurafenib alone or combined with cobimetinib), BCL2 overexpression especially in t(11:14) (targeted by venetoclax), JAK2 pathway activation (targeted by ruxolitinib), NF-kB pathway activation (treated with DANFIN combined with bortezomib), MDM2 overexpression (targeted by DS-3032b) and targeting the PI3K/mTOR pathway (targeted by BEZ235). Cyclin D1 (CCND1), and MYC are also emerging as key potential targets. In addition, histone deacetylase (HDAC) 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 anti-myeloma activity. A better understanding of th...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research