Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?

Reinaldo Franqui-Machin; Erik B Wendlandt; Siegfried Janz; Fenghuang Zhan; Guido Tricot

doi:10.18632/oncotarget.5800

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Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?

Journal article

Open access

Peer reviewed

Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?

Reinaldo Franqui-Machin, Erik B Wendlandt, Siegfried Janz, Fenghuang Zhan and Guido Tricot

Oncotarget, Vol.6(38), pp.40496-40506

12/01/2015

DOI: 10.18632/oncotarget.5800

PMCID: PMC4747348

PMID: 26415231

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Abstract

Multiple myeloma (MM) remains a largely incurable, genetically heterogeneous plasma-cell malignancy that contains - just like many other cancers - a small fraction of clonogenic stem cell-like cells that exhibit pronounced self-renewal and differentiation capacities, but also pronounced drug resistance. These MM stem cells (MMSCs) are a controversial but highly significant issue in myeloma research because, in our opinion, they are at the root of the failure of anti-neoplastic chemotherapies to transform myeloma to a manageable chronic disease. Several markers including CD138-, ALDH1+ and SP have been used to identify MMSCs; however, no single marker is reliable for the isolation of MMSC. Nonetheless, it is now known that MMSCs depend on self-renewal and pro-survival pathways, such as AKT, Wnt/β-catenin, Notch and Hedgehog, which can be targeted with novel drugs that have shown promise in pre-clinical and clinical trials. Here, we review the pathways of myeloma "stemness", the interactions with the bone marrow microenvironment that promote drug resistance, and the obstacles that must be overcome to eradicate MMSCs and make myeloma a curable disease.

Multiple Myeloma - drug therapy

Multiple Myeloma - pathology

Animals

Neoplastic Stem Cells - drug effects

Humans

Neoplastic Stem Cells - pathology

Drug Resistance, Neoplasm

Antineoplastic Agents - therapeutic use

Details

Title: Subtitle: Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction?
Creators: Reinaldo Franqui-Machin - Interdisciplinary Graduate Program in Molecular and Cellular Biology, The University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Erik B Wendlandt - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Siegfried Janz - Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Fenghuang Zhan - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Guido Tricot - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Oncotarget, Vol.6(38), pp.40496-40506
DOI: 10.18632/oncotarget.5800
PMID: 26415231
PMCID: PMC4747348
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Grant note: R01 CA152105 / NCI NIH HHS R01 CA151354 / NCI NIH HHS T32 HL007344 / NHLBI NIH HHS R01CA152105 / NCI NIH HHS R01CA151354 / NCI NIH HHS P30CA086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 12/01/2015
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
Record Identifier: 9984083281102771

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