Angiogenesis of gastrointestinal tumours and their metastases--a target for intervention?

Abstract

Angiogenesis is an obligatory event for the growth of tumours beyond 2 mm in diameter, above which simple oxygen diffusion can no longer support the rapid proliferation of malignant cells. Angiogenesis is a fine balance between inhibitory and stimulatory factors, the knowledge of which offers novel targets for the treatment of gastrointestinal neoplasia. A literature search of Pubmed and Medline databases was undertaken, using the keywords colorectal cancer, pancreatic cancer, gastrointestinal cancer, angiogenesis and anti-angiogenesis therapy. It was found that angiogenesis in primary tumours is a sequential and highly complex cascade of molecular events resulting in the rapid exponential growth of the tumour. Hepatic metastases of primary tumours may be less reliant on traditional angiogenic pathways, by co-opting pre-existing hepatic vasculature. Research into angiogenesis has revealed many different sites that can be targeted by agents such as tyrosine kinase inhibitors. Many anti-angiogenic agents are undergoing preclinical evaluation, with only a few entering phase I and phase III clinical trials. However, early results suggest that anti-angiogenic therapy could be an important adjunct to conventional chemotherapy treatment of gastrointestinal neoplasia.