Advances in Medical Research

Highlights from Houston

by Joyce Graff, Director of Wellness

The 10th International Medical Symposium on VHL was a fabulous meeting. The meeting was hosted by M.D. Anderson Cancer Center (MDACC). Co-chairs Dr. Eric Jonasch, Dr. Ian McCutcheon, and Dr. Surena Matin organized the agenda to bring together researchers working in the same area to synergize their work on VHL and move the research forward.

As we learn more about what goes on deep inside the cell, we realize that there is still more to be explored. It’s like exploring the universe of the sky, but in reverse—the universe that lives inside each cell. Just as we have had to invent new words to describe bigger dimensions—megabytes, gigabytes, terabytes—so too in the cell we have had to invent new words to describe the smaller dimensions, mechanisms, and interactions within our cells.

Most of the action in drug development, at this point, is focused on kidney cancer. Why? Because it turns out that VHL is the single most important genetic factor in creating kidney cancer—not only in VHL but also in 85% of the kidney cancer that occurs sporadically, at random in the general population. If you look inside a sporadic kidney cancer tumor, both VHL genes have been altered by some random events in order to kick off that tumor. The drug we are looking for in VHL is the drug that will help all people with kidney cancer.

There are already six new drugs approved and on the market because of VHL research. They were approved for advanced kidney cancer read—“metastatic”—that has already spread to other organs. These six drugs are also being used for breast cancer, ovarian cancer, small cell lung cancer, colon cancer—how is this? Because no matter where a cancer appears in the body, down deep inside the cell it is the same very basic set of factors that cause the cell replication to lose control, and eventually to acquire the potential to move from this one site out into the body, plant itself in other organs, and cause problems elsewhere. The key players in this process are VHL, HIF, and VEGF. They are part of an intricate system of sensors and controls inside the cell. They don’t just do one thing; they are all multi-function players. VHL, for example, senses oxygen and iron levels. When there is too little oxygen the VHL protein puts out signals that result in the building of new blood vessels to bring more oxygen. If its oxygen sensor is broken, and the VHL protein believes there is too little oxygen even though all is well, then it kicks off the process of building an excess of new blood vessels that become a hemangioma, a VHL tumor. Worse than that, when VHL is altered, the metabolic pathway in the cell gets hijacked, which then affects nearly everything.

Introducing the Kidney session, Dr. Surena Matin, urologist from MDACC, said “the VHL community has given so much to the kidney community. It is time now for us to give back.” The drugs that have been developed for advanced kidney cancer are now in their third generation. They are beginning to be the type of kinder, gentler drug that might be taken over a longer period of time to keep tumors small, or perhaps keep them from developing at all. We are not quite there yet, but we are getting there. The pazopanib trial that is open now at MDACC is one such drug, and there will be more. [See page 5]

In the early drug trials with VHL we have seen that while the kidney tumors and sometimes the pancreatic tumors do respond to the drugs, the eye, brain, and spinal tumors do not. We need to add at least one additional drug target to get the tumors of the central nervous system (CNS) to respond. Pazopanib is the first of several new drugs that incorporate additional targets.

Dr. Rachel Giles of the Netherlands summarized the first day for the group on Sunday; Joyce Graff summarized Day Two, the clinical talks. Their slides and video of their talks are available at http://vhl.org/conf2012. They will serve as a good overview and allow you to choose which of the given talks you want to explore in greater detail. The abstracts of the talks, the handouts, and the videos will be available also through vhl.org/conf2012.
The talks emphasized the improvements in surgical techniques, especially from laparoscopic to robotic surgery. Open surgery requires a very large incision. When it is possible to do one of these “percutaneous” procedures, the surgeon makes 2–5 small incisions, puts a television camera and various instruments through these “ports,” and operates beneath the skin. While the laparoscopic instruments are somewhat like working with chopsticks, the robotic instruments have a “wrist” that allows the surgeon to move in a more natural way, as with hands, so it is easier for the surgeon to master and has more capabilities than the laparoscopic instruments.

Treating eye tumors on or near the optic nerve continues to be a very large problem. Dr. Emily Chew at the US National Eye Institute is collecting cases and speaking with retinal specialists around the world to determine what works best. Ultimately, though, a drug is needed.

Methods of removing endolymphatic sac tumors (ELST) are improving, but the biggest problem is identifying them before hearing is lost, and reacting quickly enough to preserve at least a portion of the hearing. Dr. Marie Luise Bisgaard presented the work of the Danish VHL Study Group which is using annual audiology testing as a way of identifying trends, especially in low-frequency hearing loss, that might signal an ELST. She invites physicians and patients from around the world to contribute their own experiences to her study.

In a few cases, the patient may have all the symptoms of an ELST, but nothing can be seen on an MRI with thin slices through the Internal Auditory Canal (IAC) and the temporal bone. Dr. Russell Lonser and his team at the US NINDS has agreed to review the scans and possibly see patients in this situation, to determine better ways of identifying such very small ELST’s.
On Sunday a large group of patients, family members, physicians, and researchers discussed difficulties in diagnosis, problems in DNA testing, and how to serve the growing number of young people who have been diagnosed with VHL through DNA testing and preventive screening. What is the best way to serve young people, and help them take responsibility for managing their own health?

This report only scratches the surface of a very rich experience. The best part was meeting these outstanding scientists in person, watching them network and joining forces to develop enhanced methods for diagnosis and treatment of VHL related tumors. Their commitment to VHL patients is evident as they provided contact numbers and sincere offers of help. It was also wonderful to meet face-to-face and interact with people with whom we have corresponded over the internet and telephone for as much as 14 years!

We hope that you will join us for one of the meetings planned for the future which are listed in the calendar of this issue or at vhl.org/meetings. The next big Annual Meeting in the US, designed for families, is in Boston, November 17, 2012. The next International Medical Symposium will be 2014 in Madrid. See you there!

As printed in the VHL Family Forum 20:1, Winter 2012. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.