Oncotarget

Reviews:

Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms

Jahangir Abdi _, Guoan Chen and Hong Chang

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Oncotarget. 2013; 4:2186-2207. https://doi.org/10.18632/oncotarget.1497

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Abstract

Jahangir Abdi1,2, Guoan Chen3, Hong Chang1,2,4

1 Division of Immunopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

2 Dept. of Laboratory Hematology, University Health Network, Toronto, Ontario, Canada

3 Dept. of Hematology & Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China

4 Division of Molecular and Cellular Biology, Toronto General Research Institute; Toronto, Ontario, Canada

Correspondence:

Hong Chang, email:

Keywordsmultiple myeloma, drug resistance, signaling pathways, oncogenes

Received: October 13, 2013 Accepted: November 22, 2013 Published: November 24, 2013

Abstract

In the era of new and mostly effective therapeutic protocols, multiple myeloma still tends to be a hard-to-treat hematologic cancer. This hallmark of the disease is in fact a sequel to drug resistant phenotypes persisting initially or emerging in the course of treatment. Furthermore, the heterogeneous nature of multiple myeloma makes treating patients with the same drug challenging because finding a drugable oncogenic process common to all patients is not yet feasible, while our current knowledge of genetic/epigenetic basis of multiple myeloma pathogenesis is outstanding. Nonetheless, bone marrow microenvironment components are well known as playing critical roles in myeloma tumor cell survival and environment-mediated drug resistance happening most possibly in all myeloma patients. Generally speaking, however; real mechanisms underlying drug resistance in multiple myeloma are not completely understood. The present review will discuss the latest findings and concepts in this regard. It reviews the association of important chromosomal translocations, oncogenes (e.g. TP53) mutations and deranged signaling pathways (e.g. NFκB) with drug response in clinical and experimental investigations. It will also highlight how bone marrow microenvironment signals (Wnt, Notch) and myeloma cancer stem cells could contribute to drug resistance in multiple myeloma.


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