Multiple myeloma: A paradigm for translation of the cancer stem cell hypothesis

Jasmin Roya Agarwal, William Matsui

Research output: Contribution to journalArticle

Abstract

Despite recent advances in drug development, multiple myeloma (MM) remains incurable for the majority of patients due to relapse and disease progression. The cancer stem cell (CSC) hypothesis may provide an explanation for these clinical findings. It suggests that the long-term proliferative potential responsible for disease initiation, maintenance, and relapse is contained within specific subpopulations of biologically distinct tumor cells. Data in MM suggest that CSCs represent a rare cell population phenotypically resembling normal memory B cells. Compared to MM plasma cells, MM CSCs also appear to be relatively resistant to a wide variety of standard anti-cancer agents suggesting they may persist following treatment and mediate tumor re-growth and relapse. A unique property CSCs share with their normal counterparts is the potential for self-renewal that likely maintains the malignant clone over time. The development of therapeutic strategies targeting the signaling elements contributing to cancer cell self-renewal has been limited primarily because the cellular processes involved are poorly understood. However, it is common that the signaling pathway components regulating normal stem cell self-renewal are aberrantly activated in human cancers and may serve as potential therapeutic targets. One class of shared regulatory pathways are those active during normal embryonic patterning and organ formation such as Hedgehog (Hh), Notch and Wingless (Wnt), and emerging data suggest that these may play a role in CSCs. Here we review the identification and characterization of MM CSCs, the role of Hh in MM, and issues to be considered during the early clinical testing of CSC targeting agents.

Original languageEnglish (US)
Pages (from-to)116-120
Number of pages5
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume10
Issue number2
StatePublished - Feb 2010

Fingerprint

Neoplastic Stem Cells
Multiple Myeloma
Neoplasms
Recurrence
Disease Progression
B-Lymphocytes
Therapeutics
Clone Cells
Maintenance
Growth
Pharmaceutical Preparations
Population

Keywords

  • Cancer stem cells
  • Developmental pathways
  • Hedgehog
  • Multiple myeloma

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Pharmacology

Cite this

Multiple myeloma : A paradigm for translation of the cancer stem cell hypothesis. / Agarwal, Jasmin Roya; Matsui, William.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 10, No. 2, 02.2010, p. 116-120.

Research output: Contribution to journalArticle

Agarwal, Jasmin Roya ; Matsui, William. / Multiple myeloma : A paradigm for translation of the cancer stem cell hypothesis. In: Anti-Cancer Agents in Medicinal Chemistry. 2010 ; Vol. 10, No. 2. pp. 116-120.
@article{54d7385347af4cb998a857d9df444c42,
title = "Multiple myeloma: A paradigm for translation of the cancer stem cell hypothesis",
abstract = "Despite recent advances in drug development, multiple myeloma (MM) remains incurable for the majority of patients due to relapse and disease progression. The cancer stem cell (CSC) hypothesis may provide an explanation for these clinical findings. It suggests that the long-term proliferative potential responsible for disease initiation, maintenance, and relapse is contained within specific subpopulations of biologically distinct tumor cells. Data in MM suggest that CSCs represent a rare cell population phenotypically resembling normal memory B cells. Compared to MM plasma cells, MM CSCs also appear to be relatively resistant to a wide variety of standard anti-cancer agents suggesting they may persist following treatment and mediate tumor re-growth and relapse. A unique property CSCs share with their normal counterparts is the potential for self-renewal that likely maintains the malignant clone over time. The development of therapeutic strategies targeting the signaling elements contributing to cancer cell self-renewal has been limited primarily because the cellular processes involved are poorly understood. However, it is common that the signaling pathway components regulating normal stem cell self-renewal are aberrantly activated in human cancers and may serve as potential therapeutic targets. One class of shared regulatory pathways are those active during normal embryonic patterning and organ formation such as Hedgehog (Hh), Notch and Wingless (Wnt), and emerging data suggest that these may play a role in CSCs. Here we review the identification and characterization of MM CSCs, the role of Hh in MM, and issues to be considered during the early clinical testing of CSC targeting agents.",
keywords = "Cancer stem cells, Developmental pathways, Hedgehog, Multiple myeloma",
author = "Agarwal, {Jasmin Roya} and William Matsui",
year = "2010",
month = "2",
language = "English (US)",
volume = "10",
pages = "116--120",
journal = "Anti-Cancer Agents in Medicinal Chemistry",
issn = "1871-5206",
publisher = "Bentham Science Publishers B.V.",
number = "2",

}

TY - JOUR

T1 - Multiple myeloma

T2 - A paradigm for translation of the cancer stem cell hypothesis

AU - Agarwal, Jasmin Roya

AU - Matsui, William

PY - 2010/2

Y1 - 2010/2

N2 - Despite recent advances in drug development, multiple myeloma (MM) remains incurable for the majority of patients due to relapse and disease progression. The cancer stem cell (CSC) hypothesis may provide an explanation for these clinical findings. It suggests that the long-term proliferative potential responsible for disease initiation, maintenance, and relapse is contained within specific subpopulations of biologically distinct tumor cells. Data in MM suggest that CSCs represent a rare cell population phenotypically resembling normal memory B cells. Compared to MM plasma cells, MM CSCs also appear to be relatively resistant to a wide variety of standard anti-cancer agents suggesting they may persist following treatment and mediate tumor re-growth and relapse. A unique property CSCs share with their normal counterparts is the potential for self-renewal that likely maintains the malignant clone over time. The development of therapeutic strategies targeting the signaling elements contributing to cancer cell self-renewal has been limited primarily because the cellular processes involved are poorly understood. However, it is common that the signaling pathway components regulating normal stem cell self-renewal are aberrantly activated in human cancers and may serve as potential therapeutic targets. One class of shared regulatory pathways are those active during normal embryonic patterning and organ formation such as Hedgehog (Hh), Notch and Wingless (Wnt), and emerging data suggest that these may play a role in CSCs. Here we review the identification and characterization of MM CSCs, the role of Hh in MM, and issues to be considered during the early clinical testing of CSC targeting agents.

AB - Despite recent advances in drug development, multiple myeloma (MM) remains incurable for the majority of patients due to relapse and disease progression. The cancer stem cell (CSC) hypothesis may provide an explanation for these clinical findings. It suggests that the long-term proliferative potential responsible for disease initiation, maintenance, and relapse is contained within specific subpopulations of biologically distinct tumor cells. Data in MM suggest that CSCs represent a rare cell population phenotypically resembling normal memory B cells. Compared to MM plasma cells, MM CSCs also appear to be relatively resistant to a wide variety of standard anti-cancer agents suggesting they may persist following treatment and mediate tumor re-growth and relapse. A unique property CSCs share with their normal counterparts is the potential for self-renewal that likely maintains the malignant clone over time. The development of therapeutic strategies targeting the signaling elements contributing to cancer cell self-renewal has been limited primarily because the cellular processes involved are poorly understood. However, it is common that the signaling pathway components regulating normal stem cell self-renewal are aberrantly activated in human cancers and may serve as potential therapeutic targets. One class of shared regulatory pathways are those active during normal embryonic patterning and organ formation such as Hedgehog (Hh), Notch and Wingless (Wnt), and emerging data suggest that these may play a role in CSCs. Here we review the identification and characterization of MM CSCs, the role of Hh in MM, and issues to be considered during the early clinical testing of CSC targeting agents.

KW - Cancer stem cells

KW - Developmental pathways

KW - Hedgehog

KW - Multiple myeloma

UR - http://www.scopus.com/inward/record.url?scp=77950826827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950826827&partnerID=8YFLogxK

M3 - Article

C2 - 20184542

AN - SCOPUS:77950826827

VL - 10

SP - 116

EP - 120

JO - Anti-Cancer Agents in Medicinal Chemistry

JF - Anti-Cancer Agents in Medicinal Chemistry

SN - 1871-5206

IS - 2

ER -