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Sven Gläsker,1,2 Evelynn Vergauwen,2,3 Christian A Koch,4 Alexander Kutikov,4 Alexander O Vortmeyer5 1Neurosurgical Practise Lake Constance, Singen (Hohentwiel), Germany; 2Department of Neurosurgery, VUB University Medical Center Brussels, Brussels, Belgium; 3Department of Neurology, University Hospital Antwerp, Antwerp, Belgium; 4Fox Chase Cancer Center, Philadelphia, PA, USA; 5Department of Pathology, Indiana University-Purdue University, Indianapolis, IN, USACorrespondence: Sven GläskerDepartment of Neurosurgery, VUB University Medical Center Brussels, Laarbeeklaan 101, Brussels 1090, BelgiumEmail sven.glasker@vub.beAbstract: Understanding of molecular mechanisms of tumor growth has an increasing impact on the development of diagnostics and targeted therapy of human neoplasia. In this review, we summarize the current knowledge on molecular mechanisms and their clinical implications in von Hippel-Lindau (VHL) disease. This autosomal dominant tumor syndrome usually manifests in young adulthood and predisposes affected patients to the development of benign and malignant tumors of different organ systems mainly including the nervous system and internal organs. 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. Effective pharmacological therapy as well as detection of biomarkers is based on the understanding of the molecular basis of disease. The molecular basis of von Hippel-Lindau disease is the loss of function of the VHL protein and subsequent accumulation of hypoxia-inducible factor with downstream effects on cellular metabolism and differentiation. Organs affected by VHL disease may develop frank tumors. More characteristically, however, they reveal multiple separate microscopic foci of neoplastic cell proliferation. The exact mechanisms of tumorigenesis in VHL disease are, however, still not entirely understood and knowledge on biomarkers and targeted therapy is scarce.Keywords: Von Hippel-Lindau, VHL, tumor suppressor gene, neuroendocrine tumor, pancreatic tumor, pheochromocytoma, tumor formation, second hit, hemangioblastoma, renal cancer |
