Abstract
An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models
Keywords: Therapeutic sensitivity, targeted therapy, PI3K, PTEN, Akt, mTOR, radiological, xenografts, chemotherapeutic, germinal mutation
Current Pharmaceutical Design
Title:Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy
Volume: 18 Issue: 13
Author(s): James A. McCubrey, Linda S. Steelman, Stephen L. Abrams, Negin Misaghian, William H. Chappell, Jorg Basecke, Ferdinando Nicoletti, Massimo Libra, Giovanni Ligresti, Francac Stivala, Danijela Maksimovic-Ivanic, Sanja Mijatovic, Giuseppeo Montalto, Melchiorre Cervello, Piotr Laidler, Antonio Bonati, Camilla Evangelisti, Lucio Cocco and Alberto M. Martelli
Affiliation:
Keywords: Therapeutic sensitivity, targeted therapy, PI3K, PTEN, Akt, mTOR, radiological, xenografts, chemotherapeutic, germinal mutation
Abstract: An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models
Export Options
About this article
Cite this article as:
James A. McCubrey, Linda S. Steelman, Stephen L. Abrams, Negin Misaghian, William H. Chappell , Jorg Basecke, Ferdinando Nicoletti, Massimo Libra, Giovanni Ligresti, Francac Stivala, Danijela Maksimovic-Ivanic , Sanja Mijatovic, Giuseppeo Montalto, Melchiorre Cervello, Piotr Laidler, Antonio Bonati, Camilla Evangelisti, Lucio Cocco and Alberto M. Martelli , Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy , Current Pharmaceutical Design 2012; 18 (13) . https://dx.doi.org/10.2174/138161212799859701
DOI https://dx.doi.org/10.2174/138161212799859701 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Recent Advances in Elucidating Paclitaxel Resistance Mechanisms in Non-small Cell Lung Cancer and Strategies to Overcome Drug Resistance
Current Medicinal Chemistry Gene Therapy for Brain Cancer: Combination Therapies Provide Enhanced Efficacy and Safety
Current Gene Therapy Pharmacotherapy in Type 2 Diabetes: A Functional Schema for Drug Classification
Current Diabetes Reviews Mast Cells as Target in Cancer Therapy
Current Pharmaceutical Design DNA Methylation and Breast Cancer
Current Genomics Inhaled Corticosteroids in COPD: Pros and Cons
Current Drug Targets Management of Peyronie's Disease after Collagenase (Xiaflex:<sup>®</sup>)
Current Drug Targets Gene Expression Studies to Investigate Disease Mechanisms in Rheumatoid Arthritis: Does Angiogenesis Play a Role?
Current Rheumatology Reviews Editorial (Hot Topic: Inhibition of PI3K/Akt/mTOR Signaling by Natural Products)
Anti-Cancer Agents in Medicinal Chemistry Papillary Thyroid Carcinoma in Pediatric Age: An Example of a Rare Tumour Managed Within a Cooperative Comprehensive Project
Current Pediatric Reviews Challenges in Oral Delivery: Role of P-gp Efflux Pump
Current Drug Therapy Integration of DNA Methylation Data and Gene Expression Data for Prostate Adenocarcinoma: A Proof of Concept
Current Bioinformatics Metal Complexes, their Cellular Targets and Potential for Cancer Therapy
Current Pharmaceutical Design Carbohydrate Mimotopes in the Rational Design of Cancer Vaccines
Current Topics in Medicinal Chemistry Role of Nanomedicine in Hepatic Targeting- Deciphering Strategies with Molecular Insights and Preclinical Prospects
Drug Delivery Letters Basic Mechanisms Involved in the Anti-Cancer Effects of Melatonin
Current Medicinal Chemistry Curcumin: A Potential Neuroprotective Agent in Parkinson's Disease
Current Pharmaceutical Design Targeting the Bone Microenvironment in Metastatic Castration-Resistant Prostate Cancer
Current Drug Targets Functional Nanoplatforms for Enhancement of Chemotherapeutic Index
Anti-Cancer Agents in Medicinal Chemistry Contemporary Pediatric Palliative Care: Myths and Barriers to Integration into Clinical Care
Current Pediatric Reviews