Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or fiction? Oncotarget 2015 Dec 01;6(38):40496-506
Date
09/29/2015Pubmed ID
26415231Pubmed Central ID
PMC4747348DOI
10.18632/oncotarget.5800Scopus ID
2-s2.0-84950996666 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
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.
Author List
Franqui-Machin R, Wendlandt EB, Janz S, Zhan F, Tricot GAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Drug Resistance, Neoplasm
Humans
Multiple Myeloma
Neoplastic Stem Cells
