Abstract
The proteasome has been regarded as a major target for antitumor therapy in selected tumor types (i.e., multiple myeloma). Available evidence suggests that targeting the proteasome with selective compounds can represent an excellent approach for modulating the response to antitumor agents including both conventional cytotoxic agents and target-specific agents. In fact, promising drug interaction data showing synergistic effects have been reported in cellular studies, both in multiple myeloma and in solid tumors. The mechanistic bases of improved efficacy of drug combinations including bortezomib or other proteasome inhibitors and conventional cytotoxic agents have been in part unravelled and involve the capability of proteasome inhibitors to interfere with the stability of the targets of cytotoxic agents (e.g., topoisomerase inhibitors) as well as with cellular protective pathways (e.g., DNA repair and NF-kB-regulated gene expression). Moreover, the synergistic interaction of proteasome inhibitors and target-specific agents implicates a variety of mechanisms linked to the specific target (e.g., histone deacetylase) modulated by the tailored drug used in combination with the proteasome inhibitor. Several clinical studies are ongoing in an attempt to define drug combination approaches that enhance the efficacy of antitumor treatments. Considering the fast moving field of preclinical research regarding proteasome inhibition, a major contribution to the understanding of the bases of tumor response to treatment with proteasome inhibitors is expected.
Keywords: Proteasome, combination treatment, cytotoxic agents, target-specific agents.
Current Pharmaceutical Design
Title:Drug Combinations with Proteasome Inhibitors in Antitumor Therapy
Volume: 19 Issue: 22
Author(s): Laura Gatti, Valentina Zuco, Nadia Zaffaroni and Paola Perego
Affiliation:
Keywords: Proteasome, combination treatment, cytotoxic agents, target-specific agents.
Abstract: The proteasome has been regarded as a major target for antitumor therapy in selected tumor types (i.e., multiple myeloma). Available evidence suggests that targeting the proteasome with selective compounds can represent an excellent approach for modulating the response to antitumor agents including both conventional cytotoxic agents and target-specific agents. In fact, promising drug interaction data showing synergistic effects have been reported in cellular studies, both in multiple myeloma and in solid tumors. The mechanistic bases of improved efficacy of drug combinations including bortezomib or other proteasome inhibitors and conventional cytotoxic agents have been in part unravelled and involve the capability of proteasome inhibitors to interfere with the stability of the targets of cytotoxic agents (e.g., topoisomerase inhibitors) as well as with cellular protective pathways (e.g., DNA repair and NF-kB-regulated gene expression). Moreover, the synergistic interaction of proteasome inhibitors and target-specific agents implicates a variety of mechanisms linked to the specific target (e.g., histone deacetylase) modulated by the tailored drug used in combination with the proteasome inhibitor. Several clinical studies are ongoing in an attempt to define drug combination approaches that enhance the efficacy of antitumor treatments. Considering the fast moving field of preclinical research regarding proteasome inhibition, a major contribution to the understanding of the bases of tumor response to treatment with proteasome inhibitors is expected.
Export Options
About this article
Cite this article as:
Gatti Laura, Zuco Valentina, Zaffaroni Nadia and Perego Paola, Drug Combinations with Proteasome Inhibitors in Antitumor Therapy, Current Pharmaceutical Design 2013; 19 (22) . https://dx.doi.org/10.2174/1381612811319220015
DOI https://dx.doi.org/10.2174/1381612811319220015 |
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
-
Targeting the Ubiquitin-Proteasome Pathway: An Emerging Concept in Cancer Therapy
Current Topics in Medicinal Chemistry Editorial(Hot Topic:Targeting the Ubiquitin-Proteasome Pathway - Current Perspectives and Future Directions)
Current Pharmaceutical Design Alkylboronate Synthesis Based on Transition Metal-Catalyzed Hydroboration.
Current Organic Synthesis The Applicability of mTOR Inhibition in Solid Tumors
Current Cancer Drug Targets Adhesion Molecules as Targets for the Treatment of Neoplastic Diseases
Current Pharmaceutical Design Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy
Current Genomics A Five-gene Signature for Predicting the Prognosis of Colorectal Cancer
Current Gene Therapy miR-149 as a Potential Molecular Target for Cancer
Current Medicinal Chemistry Advances in Targeting Insulin-like Growth Factor Signaling Pathway in Cancer Treatment
Current Pharmaceutical Design Stem Cell Transplantation in Multiple Myeloma
Current Cancer Drug Targets Signal Transduction Therapy Targeting Apoptosis Pathways in Cancers
Current Signal Transduction Therapy A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma
Current Medicinal Chemistry The Hydroxamic Acids as Potential Anticancer and Neuroprotective Agents
Current Medicinal Chemistry Radionuclide-Labeled Peptides for Imaging and Treatment of CXCR4- Overexpressing Malignant Tumors
Current Topics in Medicinal Chemistry Epigenetic Modulation: A Promising Avenue to Advance Hematopoietic Stem Cell-Based Therapy for Severe Autoimmune Disorders
Epigenetic Diagnosis & Therapy (Discontinued) Nanomedicine: Potential Devices for Diagnostics
Recent Patents on Nanomedicine Molecular Targeting of Cell Death Signal Transduction Pathways in Cancer
Current Signal Transduction Therapy Cancer Stem Cells: The ‘Achilles Heel’ of Chemo-Resistant Tumors
Recent Patents on Anti-Cancer Drug Discovery Targeting the Phosphatidylinositol 3-Kinase/AKT Pathway for the Treatment of Multiple Myeloma
Current Medicinal Chemistry CARD Proteins as Therapeutic Targets in Cancer
Current Drug Targets