Bortezomib, dexamethasone, and fibroblast growth factor receptor 3-specific tyrosine kinase inhibitor in t(4;14) myeloma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Guido BispingJoachim Kienast

Abstract

Novel drugs including targeted approaches have changed treatment paradigms for multiple myeloma (MM) and may also have therapeutic potential in the poor-prognosis t(4;14) subset; t(4;14) results in overexpressed and activated fibroblast growth factor receptor 3 (FGFR3). Blocking this receptor tyrosine kinase (RTK) induces apoptosis in t(4;14)+ MM cells and decreases adhesion to bone marrow stromal cells (BMSC). Using combinations of novel drugs, we investigated potential enhancement of single-agent activities within the tumor cells, targeting of the marrow micromilieu, or circumvention of drug resistance in t(4;14)+ MM. We tested effects on apoptosis and related signaling pathways in the t(4;14)+ MM subset, applying drug combinations including a FGFR3 tyrosine kinase inhibitor (RTKI), the proteasome inhibitor bortezomib, and dexamethasone. RTKI, bortezomib, and dexamethasone were active as single agents in t(4;14)+ MM. RTK inhibition triggered complementary proapoptotic pathways (e.g., decrease of Mcl-1, down-regulation of p44/42 mitogen-activated protein kinase, and activation of proapoptotic stress-activated protein/c-Jun NH(2)-terminal kinases). Synergistic or additive effects were found by combinations of RTKI with dexameth...Continue Reading

Citations

Aug 21, 2009·Nature Reviews. Cancer·Mark B MeadsWilliam S Dalton
Sep 10, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Anne LemyDaniel Abramowicz
Dec 21, 2012·Laboratory Hematology : Official Publication of the International Society for Laboratory Hematology·Saeid AbrounFarahnaz Asghari
Nov 19, 2010·Expert Review of Hematology·Kenneth H Shain, William S Dalton
Feb 5, 2016·Cancer Letters·Ting Wu, Yun Dai
Dec 17, 2010·Journal of Internal Medicine·H NahiG Gahrton
Feb 4, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R Sberro-SoussanC Legendre
May 10, 2012·Cell Adhesion & Migration·Edna Cukierman, Daniel E Bassi
Dec 31, 2010·Cancer Biology & Therapy·Wan Zhang, Peng Huang
May 3, 2016·The Journal of Small Animal Practice·J GrantD Lanore
Dec 18, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Antje HascherCarsten Müller-Tidow
Jul 5, 2019·Molecular Cancer Therapeutics·Tatsushi KodamaKoichi Akashi

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