STK405759 as a combination therapy with bortezomib or dexamethasone, in in vitro and in vivo multiple myeloma models

Oncotarget
Gabriela RozicMerav Leiba

Abstract

Multiple myeloma (MM) remains an incurable hematological malignancy. Combination regimens of conventional and novel drugs have improved patient's survival. However, most patients inevitably relapse and become refractory to the current therapeutic armamentarium. We investigated the efficacy of combining the microtubule-targeting agent STK405759 with dexamethasone or bortezomib in vitro and in vivo. STK405759 combined with dexamethasone or bortezomib had synergistic cytotoxic activity in RPMIS, CAG and MM1.S human MM cell lines through activation of caspase 2, 3, 8, 9 and PARP. These treatments remained cytotoxic in the presence of bone marrow stroma cells. In other MM cells, including cells resistant to vincristine, melphalan, mitoxantrone or dexamethasone, these combinations decreased significantly survival as compared to single agents. In in vivo studies, STK405759 disrupted existing blood vessels in xenograft tumors, acting not only as a cytotoxic agent but also as an anti-angiogenic drug. Mice treated with STK405759 in combination with dexamethasone or bortezomib resulted in greater tumor growth inhibition, increased overall response and prolonged survival as compared to as compared to BTZ or DEXA alone. Their anticancer act...Continue Reading

References

Aug 1, 1986·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B G DurieJ J Costanzi
Feb 1, 1970·Journal of the Neurological Sciences·W G BradleyJ N Walton
Jun 1, 1974·Annals of Internal Medicine·S Rosenthal, S Kaufman
May 24, 1984·The New England Journal of Medicine·B BarlogieR Alexanian
Feb 1, 1995·British Journal of Cancer·H AndersonD Ryder
Jan 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J J CornelissenH M Lokhorst
Nov 20, 2002·British Journal of Haematology·Shaji KumarS Vincent Rajkumar
Oct 18, 2005·Acta Haematologica·Marianna PolitouAmin Rahemtulla
Mar 24, 2007·Experimental Hematology·Kenneth C Anderson
Apr 10, 2008·Leukemia & Lymphoma·Konstantinos AnargyrouEvangelos Terpos
Jul 8, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Nicola GiulianiSabrina Bonomini
Dec 3, 2011·Blood·Linda J Bendall
Sep 1, 2012·Case Reports in Hematology·Dalia A HamdyManal Zaidan
Jan 16, 2013·British Journal of Pharmacology·Eric Solary
Jul 3, 2015·BioMed Research International·Nirmala Chandralega KampanMagdalena Plebanski
Oct 11, 2015·Drugs·Karly P Garnock-Jones
Jan 9, 2016·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Oct 19, 2016·British Journal of Clinical Pharmacology·Darcy Bates, Alan Eastman
Oct 4, 2016·Therapeutic Advances in Hematology·Hermann Einsele, Martin Schreder
Nov 10, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Souvik BanerjeeDuane D Miller
Nov 16, 2016·The Lancet. Haematology·Morie A Gertz
Oct 17, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ying ZhangXiu-Li Guo
Nov 12, 2017·Clinical Lymphoma, Myeloma & Leukemia·Fernando Cabanillas, Bijal Shah

❮ Previous
Next ❯

Citations

Apr 11, 2020·Cancer Management and Research·Hailong FengPeng He
Feb 19, 2020·Annals of Laboratory Medicine·Yousun ChungSun Young Kong
Jan 4, 2020·Experimental Hematology·Mengyuan ZhuYuchan Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
X-Ray

Software Mentioned

FlowJo
compusyn
ZEN

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.