Abstract
Insight into the mechanisms of primary or acquired drug resistance of (hematological) malignancies is critical for the development of new treatment strategies. This review will focus on Bcl-2 and the mevalonate pathway as targets for reversal of drug resistance in multiple myeloma. The Bcl-2 protein is highly expressed in myeloma patients and in vitro studies have shown its role in the regulation of chemosensitivity, which makes Bcl-2 an attractive target for treatment. Statins are widely used for the treatment of hypercholesteremia. Several in vitro studies have shown that statins may also kill hematological malignant cells including myeloma cells. We found that lovastatin induced apoptosis in myeloma and lymphoma cells by inhibition of geranylgeranylation and subsequent down regulation of Mcl-1, probably the most important anti-apoptotic protein in myeloma. Phase 1 and 2 studies have been performed with Bcl-2 antisense oligonucleotides and high dose simvastatin in combination with chemotherapy in heavily pre-treated myeloma patients. Encouraging results from these studies may provide the framework for the future application of new treatment strategies for myeloma
Keywords: Multiple myeloma, drug resistance, apoptosis, proliferation, mevalonate pathway, geranylgeranylation, Bcl-2, Mcl-1
Current Pharmaceutical Design
Title: New Treatment Strategies for Multiple Myeloma by Targeting BCL-2 and the Mevalonate Pathway
Volume: 12 Issue: 3
Author(s): Niels W.C.J. van de Donk, Andries C. Bloem, Ellen v. d. Spek and Henk M. Lokhorst
Affiliation:
Keywords: Multiple myeloma, drug resistance, apoptosis, proliferation, mevalonate pathway, geranylgeranylation, Bcl-2, Mcl-1
Abstract: Insight into the mechanisms of primary or acquired drug resistance of (hematological) malignancies is critical for the development of new treatment strategies. This review will focus on Bcl-2 and the mevalonate pathway as targets for reversal of drug resistance in multiple myeloma. The Bcl-2 protein is highly expressed in myeloma patients and in vitro studies have shown its role in the regulation of chemosensitivity, which makes Bcl-2 an attractive target for treatment. Statins are widely used for the treatment of hypercholesteremia. Several in vitro studies have shown that statins may also kill hematological malignant cells including myeloma cells. We found that lovastatin induced apoptosis in myeloma and lymphoma cells by inhibition of geranylgeranylation and subsequent down regulation of Mcl-1, probably the most important anti-apoptotic protein in myeloma. Phase 1 and 2 studies have been performed with Bcl-2 antisense oligonucleotides and high dose simvastatin in combination with chemotherapy in heavily pre-treated myeloma patients. Encouraging results from these studies may provide the framework for the future application of new treatment strategies for myeloma
Export Options
About this article
Cite this article as:
van de Donk W.C.J. Niels, Bloem C. Andries, Spek v. d. Ellen and Lokhorst M. Henk, New Treatment Strategies for Multiple Myeloma by Targeting BCL-2 and the Mevalonate Pathway, Current Pharmaceutical Design 2006; 12 (3) . https://dx.doi.org/10.2174/138161206775201974
DOI https://dx.doi.org/10.2174/138161206775201974 |
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
-
Vascular Endothelial Growth Factor Receptors [VEGFR] as Target in
Breast Cancer Treatment: Current Status in Preclinical and Clinical
Studies and Future Directions
Current Topics in Medicinal Chemistry Urokinase Receptor (uPAR) Ligand based Recombinant Toxins for Human Cancer Therapy
Current Pharmaceutical Design Microarrays and Colon Cancer in the Road for Translational Medicine
Current Bioinformatics Pro- and Anti-Arrhythmic Effects of Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Stable Expression of the Sodium/Iodide Symporter (NIS) for anti-Cancer Gene Therapy of Glioma Cells Using a Third Generation Self-Inactivating Lentiviral Vector System in Combination with 211At
Current Radiopharmaceuticals Drugs Acting on the Beta Isoform of Human Topoisomerase II (p180)
Current Medicinal Chemistry - Anti-Cancer Agents Hyperthermia Associated Osteonecrosis in Young Patients with Pelvic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Targeted Drugs in Chronic Myeloid Leukemia
Current Medicinal Chemistry Targeting Vascular Niche by Parathyroid Hormone
Current Medicinal Chemistry A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer
Current Pediatric Reviews MicroRNAs in Organogenesis and Disease
Current Molecular Medicine Targeting of Hsp32 in Solid Tumors and Leukemias: A Novel Approach to Optimize Anticancer Therapy (Supplementry Material)
Current Cancer Drug Targets Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis
Current Genomics Demographic and Clinical Evaluation of Patients with Pancreatic Cancer in Mashhad University of Medical Sciences During 2002-2013
Current Cancer Therapy Reviews Invasive aspergillosis: adjunctive combination therapy
Mini-Reviews in Medicinal Chemistry Negative Regulation of NEDD8 Conjugation Pathway by Novel Molecules and Agents for Anticancer Therapy
Current Pharmaceutical Design A Practical Approach to Diagnosis and Treatment of Symptomatic Thromboembolic Events in Children with Acute Lymphoblastic Leukemia: Recommendations of the “Coagulation Defects” AIEOP Working Group
Recent Patents on Cardiovascular Drug Discovery Indoleamine 2,3-Dioxygenase, an Emerging Target for Anti-Cancer Therapy
Current Cancer Drug Targets Prematurely Aged Children: Molecular Alterations Leading to Hutchinson-Gilford Progeria and Werner Syndromes
Current Aging Science Fyn Kinase in Brain Diseases and Cancer: The Search for Inhibitors
Current Medicinal Chemistry