Researchers You Are Supporting 2006-07

Research is the primary pathway to finding a cure for VHL. We received seven very strong proposals this year. Of these, the Research Advisory Board recommended these three, which we hope will help accelerate the development of new treatments for VHL.

Dr. Bin Teh of the Van Andel Research Institute in Michigan and his team examined the many changes that occur in the genes in clear cell Renal Cell Carcinoma (ccRCC). The most common change is the loss of chromosome 3p, which includes the VHL gene. The VHL gene plays a biological role in the development of ccRCC -- not only in people with the condition VHL, but also in more than 60% of all kidney cancer. Most drug development so far has concentrated on VHL and angiogenesis. The second most common alteration, which occurs in 90% of the samples studied, is an increase in the expression of chromosome 5q which they call the 5qRCC gene.

Dr. Teh’s team is studying the implications of this 5qRCC gene. Their intention is to understand its relationship to VHL and to the development of cancerous tumors in ccRCC. By understanding the interaction of VHL and 5qRCC, they hope to find ways to make better drugs to counteract these effects.

It is very helpful in studying a human disease to have an “animal model” so that we can do early drug testing on mice rather than humans. In other words, if a mouse were to lose VHL protein function, it would be ideal if it would develop the same tumors – retina, brain, spinal cord, kidney, pancreas, and adrenal glands – as found in humans with this same genetic alteration. So far, the “VHL knockout mouse” models – mice with altered VHL genes – get liver hemangiomas rather than kidney ones.

Dr. Pause’s team is breeding mice that get changes in their kidneys, by introducing mutations also in other genes that have been shown to be important in the development of human RCC. This research team has created the first ever VHL mouse model in which cyst and tumor development can be observed in the target organs most commonly affected by VHL disease, In the breeding alone they are learning about the interaction of VHL with other proteins that are involved in the development of ccRCC and the acceleration of tumor growth. The team is also working to find combinations that will result in the development of tumors of the central nervous system (CNS). These models will serve an important role in testing new drug treatments to select the best candidates for human trials.

Most of us know about vaccinations that protect us from infectious diseases like polio and smallpox, but is it possible to be vaccinated against cancer? Or can we use cancer vaccines to treat existing disease? Vaccines work by introducing the infectious agent to the body to help the body develop its own defenses against the agent. Ironically, cancer tumors deceive the immune system into thinking they are not dangerous, so that the body does not mount its full defenses.

Dr. Don Bellgrau of the University of Colorado in Denver, with his collaborators Richard Duke and Alex Franzusoff, has developed a method for tricking the immune system into seeing a dangerous situation worthy of its full defensive action. This full response then causes the body to destroy the tumor. With grant funding from VHLFA, Dr. Bellgrau will provide proof of the principle that individualized vaccines can be made for specific VHL mutation types, and develop a preclinical roadmap for the rapid use of this approach to treat renal cell carcinoma in humans. Dr. Bellgrau presented an excellent talk in Boston to report on his first year of work. See the meeting report at vhl.org and a video of the complete talk at vhl.impactlearning.org

Thank you for your support of these projects!