Abstract
TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF gene superfamily, which induces apoptosis through engagement of death receptors. TRAIL is unusual as compared to the other cytokines of this family, as it interacts with a complex system of receptors consisting of two pro-apoptotic death receptors (TRAIL-R1 and TRAILR2) and three decoy receptors (TRAIL-R3, TRAIL-R4 and osteoprotegerin). Moreover, with respect to other members of the TNF superfamily, such as CD95L and TNF-α, TRAIL has generated great interest as a potential tumor-specific cancer therapeutic because as a stable soluble trimer it selectively induces apoptosis in many transformed cells but not in normal cells. Of note, TRAIL cytotoxicity is at least partially independent of the major systems involved in resistance to chemotherapy, such as p53 wild-type function and multidrug resistance (MDR) genes. Since one fundamental problem of most cancers is the development of multiple mechanisms of resistance, which progressively reduce or suppress the therapeutic efficacy of conventional chemotherapy, new therapeutic approaches that either restore the pro-apoptotic activity of chemotherapeutic drugs or by-pass the mechanisms of resistance are highly desirable. This review will focus on the potential of TRAIL for its application in the therapy of hematological malignancies, used either alone or in combination with chemotherapy. The scenario emerging from the literature is that the treatment and management of hematological malignancies will require the rational combination of TRAIL plus conventional or new drugs in a regimen that would optimize the anti-neoplastic activity in malignant cells resistant to chemotherapy through restoration of the proapoptotic activity of TRAIL.
Keywords: trail, leukemia, multiple myeloma, tumor chemoresistance, signal transduction, nf-kb, apoptosis, caspases
Current Pharmaceutical Design
Title: TNF-Related Apoptosis-Inducing Ligand (TRAIL): A Potential Candidate for Combined Treatment of Hematological Malignancies
Volume: 10 Issue: 29
Author(s): Paola Secchiero, Mauro Vaccarezza, Arianna Gonelli and Giorgio Zauli
Affiliation:
Keywords: trail, leukemia, multiple myeloma, tumor chemoresistance, signal transduction, nf-kb, apoptosis, caspases
Abstract: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF gene superfamily, which induces apoptosis through engagement of death receptors. TRAIL is unusual as compared to the other cytokines of this family, as it interacts with a complex system of receptors consisting of two pro-apoptotic death receptors (TRAIL-R1 and TRAILR2) and three decoy receptors (TRAIL-R3, TRAIL-R4 and osteoprotegerin). Moreover, with respect to other members of the TNF superfamily, such as CD95L and TNF-α, TRAIL has generated great interest as a potential tumor-specific cancer therapeutic because as a stable soluble trimer it selectively induces apoptosis in many transformed cells but not in normal cells. Of note, TRAIL cytotoxicity is at least partially independent of the major systems involved in resistance to chemotherapy, such as p53 wild-type function and multidrug resistance (MDR) genes. Since one fundamental problem of most cancers is the development of multiple mechanisms of resistance, which progressively reduce or suppress the therapeutic efficacy of conventional chemotherapy, new therapeutic approaches that either restore the pro-apoptotic activity of chemotherapeutic drugs or by-pass the mechanisms of resistance are highly desirable. This review will focus on the potential of TRAIL for its application in the therapy of hematological malignancies, used either alone or in combination with chemotherapy. The scenario emerging from the literature is that the treatment and management of hematological malignancies will require the rational combination of TRAIL plus conventional or new drugs in a regimen that would optimize the anti-neoplastic activity in malignant cells resistant to chemotherapy through restoration of the proapoptotic activity of TRAIL.
Export Options
About this article
Cite this article as:
Secchiero Paola, Vaccarezza Mauro, Gonelli Arianna and Zauli Giorgio, TNF-Related Apoptosis-Inducing Ligand (TRAIL): A Potential Candidate for Combined Treatment of Hematological Malignancies, Current Pharmaceutical Design 2004; 10 (29) . https://dx.doi.org/10.2174/1381612043382747
DOI https://dx.doi.org/10.2174/1381612043382747 |
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
-
Seek and Destroy: The Use of Natural Compounds for Targeting the Molecular Roots of Cancer
Current Drug Targets Preface
Current Pharmaceutical Biotechnology P53 Family: At the Crossroads in Cancer Therapy
Current Medicinal Chemistry Specific Immune Intervention with Monoclonal Antibodies for the Treatment of Multiple Sclerosis
Current Medicinal Chemistry Physcion and Physcion 8-O-β-D-glucopyranoside: Natural Anthraquinones with Potential Anticancer Activities
Current Drug Targets The Effect of Casein Kinase 2 Inhibition on three Leukemic Cell Lines
Current Drug Therapy Pyrrolo[2,1-c][1,4]benzodiazepine as a Scaffold for the Design and Synthesis of Anti- Tumour Drugs
Anti-Cancer Agents in Medicinal Chemistry Clinical Presentations and Diagnosis of Brucellosis
Recent Patents on Anti-Infective Drug Discovery Molecular Markers for Individualized Therapy in Colorectal Cancer: Progress Towards a Pharmacogenomics Array
Current Pharmacogenomics and Personalized Medicine Current Opinion in the Pharmaceutical Management of Irritable and Inflammatory Bowel Diseases: Role of ATP
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Heteroaromatic Pim Kinase Inhibitors Containing a Pyrazole Moiety
Recent Patents on Anti-Cancer Drug Discovery Editorial [Hot Topic: New Treatment Strategy of the Myelodysplastic Syndromes]
Current Pharmaceutical Design Optimizing Outcomes Following Allogeneic Hematopoietic Progenitor Cell Transplantation in AML: The Role of Hypomethylating Agents
Current Cancer Drug Targets Genetically Modified Dendritic Cells for Cancer Immunotherapy
Current Gene Therapy The Challenges in Moving from Ageing to Successful Longevity
Current Vascular Pharmacology Expression, Purification and Characterization of Recombinant Toxins Consisting of Truncated Gastrin 17 and Pseudomonas Exotoxin
Protein & Peptide Letters Dysregulation of LncRNAs in Placenta and Pathogenesis of Preeclampsia
Current Drug Targets Targeting the Tumor Proteasome as a Mechanism to Control the Synthesis and Bioactivity of Matrix Macromolecules
Current Molecular Medicine Editorial [Hot Topic:Strategies for Molecular-Based Treatment of Hematological Malignancies (Guest Editor: Per Ole Iversen)]
Current Drug Targets On the Power of Additional and Complex Chromosomal Aberrations in CML
Current Genomics