Abstract
Perhaps the most significant recent advance in oncology therapeutics has been the approval of various "molecularly targeted" anti-cancer drugs. Currently, there are a large number of similar drugs in early or late stage development, including antiangiogenic agents. Clinical development of such drugs suffers from several handicaps including determining whether a patients cancer expresses the target and is functionally contributing to cancer growth, monitoring biologic activity, and determining optimal biologic dose. The last problem is related to the low frequency of objective tumor responses (tumor shrinkage) caused by such drugs, or the lack of dose limiting toxicities necessary to define a maximum tolerated dose (MTD), or expression of optimal therapeutic activity at doses below the MTD, when one can be defined. These problems necessitate the development of alternative pharmacodynamic surrogate markers. Here we summarize several such promising markers for monitoring targeted antiangiogenic activity, and establishing optimal therapeutic/biologic dosing. The first is molecular - plasma VEGF - levels of which are rapidly and significantly increased in a dose dependent manner after injection of normal or tumor bearing mice with anti-VEGFR-2 antibodies. The second is a cellular marker, and more generic in nature - circulating VEGF receptor-2 positive cells found in peripheral blood, some of which may be circulating endothelial progenitor cells. Levels of such cells are suppressed in a dose dependent manner which correlate with previously determined optimal biologic/therapeutic anti-tumor activity of various antiangiogenic drugs or treatments. Finally, another promising marker we discuss is soluble VEGFR-2.
Keywords: tumor angiogenesis, antiangiogenic drugs, targeted therapies, vegf, circulating endothelial progenitor cells, metronomic chemotherapy
Current Cancer Drug Targets
Title: Cellular and Molecular Surrogate Markers to Monitor Targeted and Non- Targeted Antiangiogenic Drug Activity and Determine Optimal Biologic Dose
Volume: 5 Issue: 7
Author(s): Yuval Shaked, Guido Bocci, Raquel Munoz, Shan Man, John M.L. Ebos, Daniel J. Hicklin, Francesco Bertolini, Robert D'Amato and Robert S. Kerbel
Affiliation:
Keywords: tumor angiogenesis, antiangiogenic drugs, targeted therapies, vegf, circulating endothelial progenitor cells, metronomic chemotherapy
Abstract: Perhaps the most significant recent advance in oncology therapeutics has been the approval of various "molecularly targeted" anti-cancer drugs. Currently, there are a large number of similar drugs in early or late stage development, including antiangiogenic agents. Clinical development of such drugs suffers from several handicaps including determining whether a patients cancer expresses the target and is functionally contributing to cancer growth, monitoring biologic activity, and determining optimal biologic dose. The last problem is related to the low frequency of objective tumor responses (tumor shrinkage) caused by such drugs, or the lack of dose limiting toxicities necessary to define a maximum tolerated dose (MTD), or expression of optimal therapeutic activity at doses below the MTD, when one can be defined. These problems necessitate the development of alternative pharmacodynamic surrogate markers. Here we summarize several such promising markers for monitoring targeted antiangiogenic activity, and establishing optimal therapeutic/biologic dosing. The first is molecular - plasma VEGF - levels of which are rapidly and significantly increased in a dose dependent manner after injection of normal or tumor bearing mice with anti-VEGFR-2 antibodies. The second is a cellular marker, and more generic in nature - circulating VEGF receptor-2 positive cells found in peripheral blood, some of which may be circulating endothelial progenitor cells. Levels of such cells are suppressed in a dose dependent manner which correlate with previously determined optimal biologic/therapeutic anti-tumor activity of various antiangiogenic drugs or treatments. Finally, another promising marker we discuss is soluble VEGFR-2.
Export Options
About this article
Cite this article as:
Shaked Yuval, Bocci Guido, Munoz Raquel, Man Shan, Ebos M.L. John, Hicklin J. Daniel, Bertolini Francesco, D'Amato Robert and Kerbel S. Robert, Cellular and Molecular Surrogate Markers to Monitor Targeted and Non- Targeted Antiangiogenic Drug Activity and Determine Optimal Biologic Dose, Current Cancer Drug Targets 2005; 5 (7) . https://dx.doi.org/10.2174/156800905774574020
DOI https://dx.doi.org/10.2174/156800905774574020 |
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
-
Progesterone Receptor Agonists and Antagonists as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Drug Targeting to the Brain - A Review
Current Nanoscience Recent Advances in the Synthesis and Development of Curcumin, its Combinations and Formulations and Curcumin-like Compounds as Anti-infective Agents
Current Medicinal Chemistry Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Editorial (Thematic Issue: New Mechanisms and Targets for IBD Therapy: Translational Gastroenterology Comes of Age)
Current Drug Targets Tamoxifen as a Powerful Neuroprotectant in Experimental Stroke and Implications for Human Stroke Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Radiolabelled Molecules for Imaging the Translocator Protein (18 kDa) Using Positron Emission Tomography
Current Medicinal Chemistry Chronic Inflammation and Cancer: The Role of Endothelial Dysfunction and Vascular Inflammation
Current Pharmaceutical Design Evaluation of Hyperforin Analogues for Inhibition of 5-lipoxygenase
Medicinal Chemistry Risk Factors for Prolonged Postoperative Ileus in Adult Patients Undergoing Elective Colorectal Surgery: An Observational Cohort Study
Reviews on Recent Clinical Trials Development of Colon Specific Microspheres of Flurbiprofen for Inflammatory Bowel Disease
Current Drug Delivery Meet Our Editorial Board Member
Current Cancer Drug Targets Integrative Approaches for microRNA Target Prediction: Combining Sequence Information and the Paired mRNA and miRNA Expression Profiles
Current Bioinformatics Advances in Chemotherapy and Targeted Systemic Therapies for Urothelial Cancer
Current Drug Therapy Herbal Phytochemicals as Immunomodulators
Current Immunology Reviews (Discontinued) A Review: Hair Health, Concerns of Shampoo Ingredients and Scalp Nourishing Treatments
Current Pharmaceutical Biotechnology Targeting CD147 is a Novel Strategy for Antitumor Therapy
Current Pharmaceutical Design Application of Natural Dye Obtained from Sweet Indrajao on Fabrics
Current Biochemical Engineering (Discontinued) Cancer Pharmacogenomics: Germline DNA, Tumor DNA, or Both?
Current Pharmacogenomics Targeting RGD Recognizing Integrins: Drug Development, Biomaterial Research, Tumor Imaging and Targeting
Current Pharmaceutical Design