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Mechanisms and future directions for angiogenesis-based cancer therapies
1Department of Pathology, Stanford University Medical Center, Stanford, CA 94305, USA. anthon@leland.stanford.edu
Abstract:
Targeting angiogenesis represents a new strategy for the development of anticancer therapies. New targets derived from proliferating endothelial cells may be useful in developing anticancer drugs that prolong or stabilize the progression of tumors with minimal systemic toxicities. These drugs may also be used as novel imaging and radiommunotherapeutic agents in cancer therapy. In this review, the mechanisms and control of angiogenesis are discussed. Genetic and proteomic approaches to defining new potential targets on tumor vasculature are then summarized, followed by discussion of possible antiangiogenic treatments that may be derived from these targets and current clinical trials. Such strategies involve the use of endogenous antiangiogenic agents, chemotherapy, gene therapy, antiangiogenic radioligands, immunotherapy, and endothelial cell-based therapies. The potential biologic end points, toxicities, and resistance mechanisms to antiangiogenic agents must be considered as these therapies enter clinical trials.
Insights
Targeting tumor angiogenesis, the growth of new blood vessels, offers a novel anticancer strategy. This review explores antiangiogenic therapies, including drug development, imaging, and immunotherapy, for improved cancer treatment with reduced toxicity.
Area of Science:
- Oncology
- Vascular Biology
- Drug Discovery
Background:
- Angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
- Targeting tumor vasculature presents a promising strategy for developing novel anticancer therapies.
- Endothelial cells are key targets for antiangiogenic drug development, potentially leading to treatments with minimal systemic toxicities.
Purpose of the Study:
- To review the mechanisms and control of angiogenesis in cancer.
- To summarize genetic and proteomic approaches for identifying new targets in tumor vasculature.
- To discuss potential antiangiogenic treatments and their clinical applications.
Main Methods:
- Review of current literature on angiogenesis mechanisms and control.
- Summary of genetic and proteomic strategies for target identification.
- Analysis of various antiangiogenic treatment modalities, including endogenous agents, chemotherapy, gene therapy, immunotherapy, and endothelial cell-based therapies.
Main Results:
- Identification of proliferating endothelial cells as key targets for anticancer drug development.
- Discussion of diverse antiangiogenic strategies, including drug therapies, imaging agents, and immunotherapies.
- Consideration of clinical trials evaluating antiangiogenic agents, their endpoints, toxicities, and resistance mechanisms.
Conclusions:
- Targeting angiogenesis is a significant strategy for developing effective anticancer therapies.
- Antiangiogenic agents hold promise for prolonging or stabilizing tumor progression with reduced toxicity.
- Further research into biological endpoints, toxicities, and resistance mechanisms is crucial for advancing antiangiogenic therapies in clinical trials.