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: Multiple myeloma, cancer stem cells, Hedgehog, developmental pathways
Anti-Cancer Agents in Medicinal Chemistry
Title: Multiple Myeloma: A Paradigm for Translation of the Cancer Stem Cell Hypothesis
Volume: 10 Issue: 2
Author(s): Jasmin Roya Agarwal and William Matsui
Affiliation:
Keywords: Multiple myeloma, cancer stem cells, Hedgehog, developmental pathways
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.
Export Options
About this article
Cite this article as:
Agarwal Roya Jasmin and Matsui William, Multiple Myeloma: A Paradigm for Translation of the Cancer Stem Cell Hypothesis, Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (2) . https://dx.doi.org/10.2174/187152010790909344
DOI https://dx.doi.org/10.2174/187152010790909344 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Exploitation of Toll-like Receptor 3 Signaling in Cancer Therapy
Current Pharmaceutical Design A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity
Current Medicinal Chemistry An Association between MicroRNA-21 Expression and Vitamin D Deficiency in Coronary Artery Disease
MicroRNA Targeted Therapy in Advanced Gastric Carcinoma: The Future is Beginning
Current Medicinal Chemistry The Roles of miR-25 and its Targeted Genes in Development of Human Cancer
MicroRNA Targeting Heparan Sulfate Proteoglycans and their Modifying Enzymes to Enhance Anticancer Chemotherapy Efficacy and Overcome Drug Resistance
Current Medicinal Chemistry Genetic and Epigenetic Studies for Determining Molecular Targets of Natural Product Anticancer Agents
Current Cancer Drug Targets Tumor-Targeting Peptides and Small Molecules as Anti-Cancer Agents to Overcome Drug Resistance
Current Medicinal Chemistry Support Vector Machine Based Prediction of P. falciparum Proteasome Inhibitors and Development of Focused Library by Molecular Docking
Combinatorial Chemistry & High Throughput Screening Clinical Studies with Bismuth-213 and Actinium-225 for Hematologic Malignancies
Current Radiopharmaceuticals Angiopoietin-2 Axis Inhibitors: Current Status and Future Considerations for Cancer Therapy
Current Angiogenesis (Discontinued) Novel Concepts for Anti-Infective Activity of Cytokines, Chemokines and Diverse Agents
Recent Patents on Anti-Infective Drug Discovery The Autism Candidate Gene Neurobeachin Encodes a Scaffolding Protein Implicated in Membrane Trafficking and Signaling
Current Molecular Medicine Bortezomib as the First Proteasome Inhibitor Anticancer Drug: Current Status and Future Perspectives
Current Cancer Drug Targets RNA Splicing: Basic Aspects Underlie Antitumor Targeting
Recent Patents on Anti-Cancer Drug Discovery Current Drug Therapy for Prostate Cancer: An Overview
Current Medicinal Chemistry - Anti-Cancer Agents Developing FGFR4 Inhibitors As Potential Anti-Cancer Agents Via In Silico Design, Supported by In Vitro and Cell-Based Testing
Current Medicinal Chemistry Interleukin-21 in Immune and Allergic Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Targeting Angiogenic Genes as a Therapeutic Approach for Hepatocellular Carcinoma
Current Gene Therapy Aminophosphonate Metal Complexes of Biomedical Potential
Current Medicinal Chemistry