Recent advances in the understanding of tumor angiogenesis suggest that anti-angiogenesis therapy may offer a novel approach to controlling tumor growth in cancer patients. In particular, the rapidly accumulating information about endothelial growth factors suggests that they may well offer new targets for antiangiogenesis.

Angiogenesis, or the growth of new blood vessels, has been shown to be important in feeding a variety of tumors, including cancer of the breast, kidney, prostate, colon, and brain, as well as melanoma. But not all anti-angiogenesis drugs are appropriate to all types of cancers. As we read articles in the press, it is somewhat difficult to tell which ones may potentially be helpful against the tumors of VHL.

There are also drugs that help with epithelial cells (e.g. lung). These are unlikely to be useful with VHL, which involves endothelial cell growth.

Endothelial growth factors appear to be tumor specific. Therefore, it is important to understand the role of each endothelial growth factor in human tumors.

Basic fibroblast growth factor (bFGF), of which at least eight different versions have been identified, is the most potent promoter of division of the cell nucleus. bFGF appears to be fully involved in new vessel formation and is able to induce several processes. It is localized in neural cells, keratinocytes, macrophages, and endothelial cells, and has been found in tumors associated with cancers of the brain, pancras, bladder, and prostate. It is not common in other types of tumors such as breast and gastrointestinal cancer or VHL.

Vascular endothelial growth factor (VEGF), which is characterized as a vascular permeability factor with a potency some 50,000 times higher than that of histamine, is frequently and markedly up-regulated (that is, in abundant supply), in a wide variety of tumor cells, including kidney, breast, ovary, stomach, lung, bladder, head and neck cancers and glioblastoma cells. Data strongly suggest that VEGF may directly promote the growth of new blood vessels in tumor tissues. Studies have also demonstrated a possible synergy between VEGF and bFGF. The majority of work on VHL is around VEGF and related mechanisms in the cell.

Platelet-derived endothelial cell-growth factor (PD-ECGF) is increased in breast, stomach, colon, head and neck tumors. Studies have suggested a cooperative function of PD-ECGF and VEGF for new vessel formation.

Hepatocyte growth factor (HGF) can act not only on hepatocyte growth, but also on the growth of other types of cells, including endothelial cells. Few data have been published on the relationship between HGF and microvessel formation in tumor tissues.

Antiangiogenesis therapy, first suggested more than two decades ago, offers a number of benefits over conventional anticancer therapies: tumor specificity, easy accessibility, less possibility of resistance, effectiveness in combination with conventional treatments, and possible use as a way of preventing tumors.

There are two anti-angiogenic drugs currently in early stages of clinical trials for use with VHL. Progress will be reported here and on the VHL website.

As printed in the VHL Family Forum 7:2, June 1999. For permission to reprint, please contact VHL Family Alliance, info@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.

research