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Angiogenesis and Cancer Control: From Concept to Therapeutic Trial
Brem1
1Neurooncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
Abstract:
BACKGROUND: There is extraordinary interest in developing angiosuppressive agents for cancer treatment. Several new agents appear promising for the treatment of a variety of human cancers. Current concepts and new agents in clinical trials are the focus of this article. In particular, the introduction of a new treatment for human brain tumors is presented in detail, using an antiangiogenic agent, penicillamine, and depletion of an obligatory cofactor of angiogenesis, copper. METHODS: The explosive increase in literature on antiangiogenesis is reviewed using computerized search, findings presented at the recent national cancer and angiogenesis meetings. A specific protocol, NABTT 97-04, "Penicillamine and Copper Reduction for Newly Diagnosed Glioblastoma," is presented as an example of angiotherapeutic drug discovery. RESULTS: A number of promising molecular approaches are being introduced to suppress tumor angiogenesis. Major categories of angiogenesis antagonists include protease inhibitors, direct inhibitors of endothelial cell proliferation and migration, suppression of angiogenic growth factors, inhibition of endothelial-specific integrin/ survival signaling, chelators of copper, and inhibitors with specific other mechanisms. The preliminary results of early trials offer a glimpse into how antiangiogenesis therapy will be integrated into future care of the patient with cancer. CONCLUSIONS: Thirty-five antiangiogenesis therapies are currently being evaluated in clinical trials. As we learn more about the fundamental mechanisms of angiogenesis, eg, the role of copper in growth factor activation, effective methods of cancer control will be implemented.
Insights
New antiangiogenic agents show promise for cancer treatment, including a novel approach for brain tumors using penicillamine and copper reduction. Further research into angiogenesis mechanisms will improve cancer control strategies.
Area of Science:
- Oncology
- Angiogenesis research
- Cancer therapy development
Background:
- Growing interest in developing angiosuppressive agents for various human cancers.
- Emerging antiangiogenic agents show promise in preclinical and clinical settings.
- Focus on current concepts and novel agents undergoing clinical trials.
Purpose of the Study:
- To review current concepts and new agents in cancer antiangiogenesis therapy.
- To detail a novel treatment protocol for human brain tumors using antiangiogenic agents.
- To present penicillamine and copper depletion as a therapeutic strategy.
Main Methods:
- Comprehensive literature review using computerized search.
- Analysis of findings presented at national cancer and angiogenesis meetings.
- Detailed examination of the NABTT 97-04 protocol for glioblastoma treatment.
Main Results:
- Identification of multiple promising molecular approaches to suppress tumor angiogenesis.
- Categorization of angiogenesis antagonists including protease inhibitors and copper chelators.
- Preliminary trial results suggest a future role for antiangiogenesis therapy in cancer care.
Conclusions:
- Thirty-five antiangiogenesis therapies are currently under evaluation in clinical trials.
- Understanding angiogenesis mechanisms, such as copper's role in growth factor activation, is crucial.
- Effective cancer control methods will be implemented as knowledge of angiogenesis advances.