Abstract
In search of new strategies for the treatment of cancer, the interaction between tumor and stroma attracts more and more attention. Disruption of stroma functions, e.g. angiogenesis, has evolved into a promising target for cancer therapies. Since stromal cells are genetically stable, stroma-targeted therapies seem to be less susceptible to the development of drug resistance. Several well-established drugs, which had initially been developed for other indications, also exhibit antitumor activity. Among those, PPARγ agonists, COX-2 inhibitors, and mTOR antagonists are the most remarkable examples. Current research data and clinical experience suggest that these drugs target stroma functions in cancer, in particular angiogenesis, but immunological mechanisms and direct antitumor effects seem to participate as well. In addition to these drugs, frequent administration of low-dose chemotherapeutics, referred to as metronomic chemotherapy, reveals profound anti-angiogenic effects. In the meantime, a multitude of preclinical and clinical studies have been undertaken, which demonstrate the efficacy of these drugs in cancer therapy. Combinatorial use of these agents has been suggested to be superior in terms of antitumor efficacy and prevention of drug resistance. The toxicity of these therapies is surprisingly low compared with conventional high-dose chemotherapy regimens. Patients with advanced disease, often heavily pretreated and presenting multiple drug resistance, could particularly profit from such tumor-stroma-targeted therapies. However, larger randomized clinical trials are required for further evaluation and optimization of this concept.
Keywords: tumor-stroma interaction, stroma-targeted therapy, cox, mtor, rapamycin, metronomic chemotherapy, tumor angiogenesis, antiangiogenic
Current Cancer Drug Targets
Title: New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy
Volume: 5 Issue: 6
Author(s): Christian Hafner, Albrecht Reichle and Thomas Vogt
Affiliation:
Keywords: tumor-stroma interaction, stroma-targeted therapy, cox, mtor, rapamycin, metronomic chemotherapy, tumor angiogenesis, antiangiogenic
Abstract: In search of new strategies for the treatment of cancer, the interaction between tumor and stroma attracts more and more attention. Disruption of stroma functions, e.g. angiogenesis, has evolved into a promising target for cancer therapies. Since stromal cells are genetically stable, stroma-targeted therapies seem to be less susceptible to the development of drug resistance. Several well-established drugs, which had initially been developed for other indications, also exhibit antitumor activity. Among those, PPARγ agonists, COX-2 inhibitors, and mTOR antagonists are the most remarkable examples. Current research data and clinical experience suggest that these drugs target stroma functions in cancer, in particular angiogenesis, but immunological mechanisms and direct antitumor effects seem to participate as well. In addition to these drugs, frequent administration of low-dose chemotherapeutics, referred to as metronomic chemotherapy, reveals profound anti-angiogenic effects. In the meantime, a multitude of preclinical and clinical studies have been undertaken, which demonstrate the efficacy of these drugs in cancer therapy. Combinatorial use of these agents has been suggested to be superior in terms of antitumor efficacy and prevention of drug resistance. The toxicity of these therapies is surprisingly low compared with conventional high-dose chemotherapy regimens. Patients with advanced disease, often heavily pretreated and presenting multiple drug resistance, could particularly profit from such tumor-stroma-targeted therapies. However, larger randomized clinical trials are required for further evaluation and optimization of this concept.
Export Options
About this article
Cite this article as:
Hafner Christian, Reichle Albrecht and Vogt Thomas, New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy, Current Cancer Drug Targets 2005; 5 (6) . https://dx.doi.org/10.2174/1568009054863591
DOI https://dx.doi.org/10.2174/1568009054863591 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Natural Flora and Anticancer Regime: Milestones and Roadmap
Anti-Cancer Agents in Medicinal Chemistry Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology Evolution of the Strategies for Screening and Identifying Human Tumor Antigens
Current Protein & Peptide Science Intracellular Trafficking of MDR Transporters and Relevance of SNPs
Current Topics in Medicinal Chemistry Duloxetine in the Treatment of Depression: An Overview
Central Nervous System Agents in Medicinal Chemistry Approaching Neurological Diseases to Reduce Mobility Limitations in Older Persons
Current Pharmaceutical Design Liposomal Doxorubicin Delivery Systems: Effects of Formulation and Processing Parameters on Drug Loading and Release Behavior
Current Drug Delivery Recent Advances of Metallocenes for Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Drug Delivery Systems for Chemotherapeutics through Selected Polysaccharidic Vehicles
Current Organic Chemistry Recurrence in Bladder Cancer: A Molecular Dead End?
Current Genomics Berberine Exhibits Antitumor Effects in Human Ovarian Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Targeting Heme for the Identification of Cytotoxic Agents
Anti-Cancer Agents in Medicinal Chemistry Exosomes: A Role for Naturally Occurring Nanovesicles in Cancer Growth, Diagnosis and Treatment
Current Gene Therapy Botulinum Toxin: Pharmacology and Clinical Developments: A Literature Review
Medicinal Chemistry New Insights Toward Nanostructured Drug Delivery of Plant-Derived Polyphenol Compounds: Cancer Treatment and Gene Expression Profiles
Current Cancer Drug Targets Fiber-Optic Technologies in Laser-Based Therapeutics: Threads for a Cure
Current Pharmaceutical Biotechnology Pleiotrophin as a Possible New Target for Angiogenesis-Related Diseases and Cancer
Recent Patents on Anti-Cancer Drug Discovery Radiolabelled Probes Targeting Tumor Hypoxia for Personalized Medicine
Current Pharmaceutical Design Plant Derived Inhibitor Sulforaphane in Combinatorial Therapy Against Therapeutically Challenging Pancreatic Cancer
Anti-Cancer Agents in Medicinal Chemistry Ricin and Saporin: Plant Enzymes for the Research and the Clinics
Current Chemical Biology