Abstract
Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.
Keywords: Cancer, combination treatment, targeted agents, preclinical development, chemotherapy
Current Cancer Drug Targets
Title: Development and Assessment of Conventional and Targeted Drug Combinations for Use in the Treatment of Aggressive Breast Cancers
Volume: 6 Issue: 6
Author(s): D. N. Waterhouse, K. A. Gelmon, R. Klasa, K. Chi, D. Huntsman, E. Ramsay, E. Wasan, L. Edwards, C. Tucker, J. Zastre, Y. Z. Zhang, D. Yapp, W. Dragowska, S. Dedha and M. B. Bally
Affiliation:
Keywords: Cancer, combination treatment, targeted agents, preclinical development, chemotherapy
Abstract: Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.
Export Options
About this article
Cite this article as:
Waterhouse N. D., Gelmon A. K., Klasa R., Chi K., Huntsman D., Ramsay E., Wasan E., Edwards L., Tucker C., Zastre J., Zhang Z. Y., Yapp D., Dragowska W., Dedha S. and Bally B. M., Development and Assessment of Conventional and Targeted Drug Combinations for Use in the Treatment of Aggressive Breast Cancers, Current Cancer Drug Targets 2006; 6 (6) . https://dx.doi.org/10.2174/156800906778194586
DOI https://dx.doi.org/10.2174/156800906778194586 |
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
-
Thiopurine S-Methyltransferase as a Pharmacogenetic Biomarker: Significance of Testing and Review of Major Methods
Cardiovascular & Hematological Agents in Medicinal Chemistry Mitochondrial Respiratory Complex I: Structure, Function and Implication in Human Diseases
Current Medicinal Chemistry Chemotherapy-Induced Modifications to Gastrointestinal Microflora: Evidence and Implications of Change
Current Drug Metabolism Updates on the Role of FDG-PET/CT in Gynecological Malignancies
Current Molecular Imaging (Discontinued) Tumor Biomarkers: Clinical Utility, Promises and Problems
Applied Clinical Research, Clinical Trials and Regulatory Affairs Pharmacological Modulation of Th17
Recent Patents on Inflammation & Allergy Drug Discovery Nitroimidazole Radiopharmaceuticals in Hypoxia: Part II Cytotoxicity and Radiosensitization Applications
Current Radiopharmaceuticals Dehydroleucodine Induces a TP73-dependent Transcriptional Regulation of Multiple Cell Death Target Genes in Human Glioblastoma Cells
Anti-Cancer Agents in Medicinal Chemistry Quassinoids: From Traditional Drugs to New Cancer Therapeutics
Current Medicinal Chemistry Bombacaceae Between the Ethnomedical Uses and Pharmacological Evidences: A Review
The Natural Products Journal Patented Herbal Formulations and their Therapeutic Applications
Recent Patents on Drug Delivery & Formulation Epigenetics in Clinical Management of Children and Adolescents with Brain Tumors
Current Cancer Drug Targets Localised Delivery of Therapeutic Agents to CNS Malignancies: Old and New Approaches
Current Pharmaceutical Biotechnology Cardiovascular Effects of the Phytoestrogen Genistein
Current Medicinal Chemistry - Cardiovascular & Hematological Agents The Gene Expression Profiles of Medulloblastoma Cell Lines Resistant to Preactivated Cyclophosphamide
Current Cancer Drug Targets Effect of PI3K/AKT/mTOR Signaling Pathway on Regulating and Controlling the Anti-Invasion and Metastasis of Hepatoma Cells by Bufalin
Recent Patents on Anti-Cancer Drug Discovery Lemon Juice as a Biocatalyst Under Ultrasound Irradiation: Synthesis and Pharmacological Evaluation of 2-amino 1,3,4-thiadiazoles
Anti-Cancer Agents in Medicinal Chemistry Possible Involvement of Angiogenesis in Chronic Liver Diseases: Interaction Among Renin-Angiotensin-Aldosterone System, Insulin Resistance and Oxidative Stress
Current Medicinal Chemistry Assays for Eukaryotic Cell Chemotaxis
Combinatorial Chemistry & High Throughput Screening Glycoprotein Targeting and Other Applications of Lectins in Biotechnology
Current Protein & Peptide Science