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Updated: Aug 7, 2026
04:48
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Current development status of small-molecule vascular disrupting agents
David J Chaplin1, Michael R Horsman, Dietmar W Siemann
1OXiGENE Inc, 230 Third Avenue, Waltham, MA 02451, USA. dchaplin@oxigene.com
Current Opinion in Investigational Drugs (London, England : 2000)
|June 21, 2006
Summary
Small-molecule vascular disrupting agents (VDAs) show promise in cancer therapy by selectively targeting abnormal blood vessels. Clinical trials are evaluating VDAs, like CA4P and DMXAA, for combination treatments.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Abnormal vasculature is a hallmark of diseases like cancer and macular degeneration.
- Small-molecule vascular disrupting agents (VDAs) offer a novel therapeutic strategy distinct from anti-angiogenesis.
- VDAs selectively target and disrupt existing abnormal blood vessels.
Purpose of the Study:
- To review small-molecule VDAs currently in clinical development.
- To discuss the potential of VDAs in combination with traditional cancer therapies.
- To highlight the distinct mechanism of action of VDAs compared to anti-angiogenic agents.
Main Methods:
- Review of clinical trial data for VDAs.
- Analysis of preclinical studies on VDA efficacy.
- Examination of two main VDA drug classes: tubulin binders and flavonoids.
Main Results:
- Phase I studies confirm VDAs selectively reduce tumor blood flow at well-tolerated doses.
- Preclinical data suggest VDAs enhance tumor response to chemotherapy, radiation, and anti-angiogenics.
- VDAs are effective in destroying central tumor regions, potentially overcoming therapy resistance.
Conclusions:
- Small-molecule VDAs are a promising class of drugs for cancer treatment.
- Combination therapy with VDAs and conventional treatments (chemotherapy, radiation, anti-angiogenics) shows significant potential.
- VDAs like combretastatin A4 phosphate (CA4P) and 5,6-dimethylxantlenone-4-acetic acid (DMXAA) are advancing in clinical trials.
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