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Endogenous angiogenesis inhibitors
1Departments of Surgery, Children's Hospital and Harvard Medical School and Vascular Biology Program, Children's Hospital, Boston, Massachusetts 02115, USA. judah.folkman@childrens.harvard.edu
Abstract:
When the FDA commissioner announced in February 2004 the approval of Avastin for the treatment of patients with colon cancer, he called angiogenesis inhibitors a fourth modality of anti-cancer therapy. Because angiogenesis inhibitors are relatively less toxic than conventional chemotherapy and have a lower risk of drug resistance, they may also represent a new class of anti-cancer agents, some of which have sufficiently reduced toxicity that they may be safely used long term. These include immunotherapy, vaccines, telomerase inhibitors, apoptosis inducers, low dose metronomic chemotherapy, novel hormonal therapies, gene therapy and others. However, at least 16 endogenous angiogenesis inhibitors have been discovered in the circulation, and/or in the extracellular matrix. These may become the safest and least toxic of anti-cancer therapies. Four are already being administered by injection in clinical trials for cancer. Recently, it has been reported that at least two endogenous angiogenesis inhibitors can be significantly increased in humans (endostatin), and in mice (thrombospondin), by oral administration of small molecules which themselves are already FDA approved for other uses. This finding suggests several new clinical applications for the future, including the possibility of guiding the use of angiogenesis inhibitors by blood or urinary biomarkers, currently being developed, that may detect the presence of cancer before it is symptomatic, or before it can be located by conventional methods.
Insights
Angiogenesis inhibitors, a novel cancer therapy, show promise for long-term use due to lower toxicity. Endogenous inhibitors, boosted by existing drugs, may offer safer treatments and early cancer detection via biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Angiogenesis inhibitors represent a fourth modality of anti-cancer therapy, offering reduced toxicity and drug resistance compared to conventional chemotherapy.
- Several endogenous angiogenesis inhibitors exist, with potential for safer, long-term cancer treatment and clinical trials underway.
Purpose of the Study:
- To explore the potential of endogenous angiogenesis inhibitors as safe and effective anti-cancer therapies.
- To investigate novel methods for increasing endogenous angiogenesis inhibitor levels for therapeutic benefit.
- To assess the feasibility of using biomarkers for early cancer detection guided by angiogenesis inhibitor levels.
Main Methods:
- Review of existing literature on angiogenesis inhibitors, including endogenous forms.
- Analysis of recent findings on orally administered small molecules increasing endogenous angiogenesis inhibitors (endostatin, thrombospondin).
- Discussion of emerging blood or urinary biomarkers for cancer detection.
Main Results:
- Endogenous angiogenesis inhibitors show potential as the safest and least toxic anti-cancer agents.
- Oral administration of FDA-approved small molecules can significantly increase levels of endogenous angiogenesis inhibitors.
- Development of biomarkers may enable early cancer detection before symptoms or conventional localization.
Conclusions:
- Endogenous angiogenesis inhibitors represent a promising avenue for developing safer, long-term cancer therapies.
- Existing FDA-approved drugs could be repurposed to enhance endogenous angiogenesis inhibitor production.
- Biomarker-guided angiogenesis inhibitor therapy holds potential for early cancer detection and personalized treatment.
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