One Biomarker for Angiogenesis

en français

During the first six months of 2005, researchers from the laboratory of Dr. John Heymach and Dr. Judah Folkman at Dana Farber Cancer Research Center in Boston analyzed blood samples from a number of clinical trials, including the PTK trial, trying to find a biomarker that would be useful in tracking the effect of anti-angiogenic therapy.

A biomarker is a chemical in the blood or urine that can be tested to indicate whether the treatment is improving the situation, or whether there is cause for concern. One example of a biomarker is the PSA test for prostate cancer in men. If the PSA levels are elevated, there is cause for concern, and additional tests are done to determine just what is going on.

In this case, the researchers are looking for a way to get a quick indication whether the amount of tumor is growing or receding, indicating whether the treatment is shrinking the tumor, or whether the tumor is still growing. Again, it's not the final answer, but it is an indication that can be gotten easily, without expensive scans.

In this study, they were looking at the levels of circulating endothelial cells in the blood stream. These are usually found in the lining of blood vessels. If they have been released into the blood stream they are of one of two types:

• CEPs, newly formed cells released from the bone marrow, on their way to becoming blood vessels (indicating that blood vessels are being formed); or
• CECs, mature cells released from the blood vessels, on their way to degradation, indicating that blood vessels are being destroyed.

A modest number of both are a normal part of the body's self-repair and renewal, but higher levels might indicate whether anti-angiogenic therapy is working.

In analyzing the pre-treatment blood samples, they noticed a very distinct difference between the blood samples from people with VHL, and other subjects in other trials. In most people, the normal levels of progenitor cells were very low, sometimes so low it was difficult to count them. In the 7 people with VHL who participated in the PTK study, the levels of progenitor cells was significantly higher.

They asked VHLFA to invite people with VHL in the Boston area to donate blood samples to give them a larger number of samples to analyze. Fifteen people generously donated their time and blood to this research. Because the samples needed to be processed fresh on the same day, volunteers had to come on the same day to the lab.

The team concluded that this is indeed a promising way of checking on the effectiveness of anti-angiogenic therapy. CECs went way up following radio frequency ablation, indicating that the blood vessels in the tumor were dying. It may also be useful someday for detecting the presence of renal cell carcinoma -- alerting the doctor to the need for follow-up in the same way that a PSA test calls for follow-up for prostate cancer.

In reporting his results, Dr. Heymach thanked the VHL Family Alliance and these volunteers for their help in making this research possible.

References: Beaudry et al., Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity. Clin Cancer Res. 2005 May 1;11(9):3514-22. PMID: 15867254

As printed in the VHL Family Forum 13:2, August/September 2005. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.