Philadelphia International Medicine
Fox Chase Researchers Collaborate With International Team on Review of Von Hippel-Lindau Disease
PHILADELPHIA (July 27, 2020)—In a recent review article, Fox Chase Cancer Center researchers outlined obstacles, research methods, and future treatment prospects for patients with Von Hippel-Lindau (VHL) disease.
VHL is a rare hereditary tumor syndrome that involves the abnormal growth of both benign and malignant tumors in various parts of the body, including the nervous system and internal organs. It occurs when an individual carries a germline mutation of the VHL tumor suppressor gene. The disorder usually presents itself in young adulthood and affects about one in every 36,000 people.
“A consequent screening and timely preventive treatment of lesions are crucial for patients affected by VHL disease. Surgical indications and treatment have been evaluated and optimized over many years. In the last decade, pharmacological therapies have been evolving, but are largely still at an experimental stage,” the authors wrote.
The paper reviews and summarizes for the first time the work that has been done for this syndrome, including research on oncological targets as well as manifestations and possible biomarkers, said Christian A. Koch, MD, PhD, FACP, MACE, director of the Section of Endocrinology in the Department of Medicine at Fox Chase.
Koch worked on the paper with Alexander Kutikov, MD, FACS, chief of the Division of Urology and Urologic Oncology at Fox Chase. They collaborated with leading VHL researchers from facilities in Indiana, Belgium, and Germany, including lead author Sven Gläsker, MD, a neurosurgeon who serves on the clinical advisory council of the VHL Alliance.
“The research we’ve done involved loss of heterozygosity studies, which means we looked at micro-dissected tumor tissue and compared it to a control sample from the same patient’s blood or normal tissue. From there we can figure out which germline mutation the patient has and how tumor evolution possibly occurs,” Koch said.
The challenge then and now is for researchers to look at tissue and learn what to target in VHL patients by identifying precursor lesions that could potentially turn into tumors, he added. A thought leader in that work and senior author of the paper is Alexander O. Vortmeyer, MD, of Indiana University.
The authors said agents, including sorafenib, thalidomide, HIF2α, octreotide, and immunotherapeutic approaches, are among some of the treatments that may seem promising, but more studies need to be done for safety and efficacy.
“If you know the signaling pathways and genetic-accumulating mutations, then you can target them,” said Koch. “Otherwise, we do what we do now for Von Hippel-Lindau, which is try some other therapies and see what’s working, as reviewed in our paper by neurology resident Evelynn Vergauwen. I think this paper demonstrates that there is light on the horizon for Von Hippel-Lindau disease.”
The review, “Von Hippel-Lindau Disease: Current Challenges and Future Prospects,” was published in the journal OncoTargets and Therapy.