Antivascular therapy: a new approach to cancer treatmentBMJ 1999; 318 doi: http://dx.doi.org/10.1136/bmj.318.7187.853 (Published 27 March 1999) Cite this as: BMJ 1999;318:853
- A J Hayes, surgical registrar ([email protected]),
- L Y Li, assistant professor of biochemistry,
- M E Lippman, professor of medicine and pharmacology
- Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, Washington DC, 20007, USA
- Correspondence to: Dr Hayes
The understanding that the growth of tumours is dependent on angiogenesis has led to the development of new approaches to treatment and new agents directed at tumour vasculature. These have yielded striking successes in experimental models, which if translated into the clinical setting will have a substantial effect on patient survival. Such new approaches are vital because, although great strides have occurred in the treatment of certain cancers, the overall standardised mortality from most solid tumours has altered little over the past two decades.1
This article considers the process of tumour angiogenesis and discusses the potential of angiogenic inhibitors as therapeutic agents.
Role of angiogenesis in growth of tumours
The vascularity of tumours has been noted for many years.2 Alguire noted that vascularisation was instigated by the developing tumour: “An outstanding characteristic of the growing tumour is its capacity to elicit the production of a new capillary endothelium from the host.”3 Tannock elegantly showed that the rate of division of tumour cells decreased in proportion to their distance from the supplying blood vessel and related this to diminishing oxygen supply.4 Moreover, he showed that the overall rate of growth was dictated not by proliferation of tumour cells but by the lower rate of proliferation of endothelial cells, concluding that the supply of oxygen and nutrients to the tumour limited its growth.
Research will clarify the mechanisms by which endogenous inhibitors of angiogenesis prevent tumour growth
Strategies will be developed for large scale production of antivascular drugs for clinical use
New treatment regimens will be developed to modify the balance of positive and negative angiogenic proteins in tumours
Extensive clinical evaluation of new antivascular treatments alongside traditional treatments will define their anticancer potential more clearly
New trials and treatments will focus on inducing long term remission
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