Gläsker Sven, Vergauwen Evelynn, Koch Christian A, Kutikov Alexander, Vortmeyer Alexander O
Neurosurgical Practise Lake Constance, Singen (Hohentwiel), Germany.
Department of Neurosurgery, VUB University Medical Center Brussels, Brussels, Belgium.
Onco Targets Ther. 2020 Jun 16;13:5669-5690. doi: 10.2147/OTT.S190753. eCollection 2020.
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.
对肿瘤生长分子机制的理解对人类肿瘤的诊断和靶向治疗发展的影响日益增大。在本综述中，我们总结了目前关于分子机制及其在冯·希佩尔-林道（VHL）病中的临床意义的知识。这种常染色体显性肿瘤综合征通常在青年期出现，使受影响患者易患不同器官系统的良性和恶性肿瘤，主要包括神经系统和内脏器官。因此，对VHL病患者进行筛查并及时进行预防性治疗至关重要。多年来，手术指征和治疗方法已得到评估和优化。在过去十年中，药物治疗一直在发展，但大多仍处于实验阶段。有效的药物治疗以及生物标志物的检测基于对疾病分子基础的理解。冯·希佩尔-林道病的分子基础是VHL蛋白功能丧失以及随后缺氧诱导因子的积累，对细胞代谢和分化产生下游影响。受VHL病影响的器官可能会发展为明显的肿瘤。然而，更典型的是，它们会出现多个独立的肿瘤细胞增殖微观病灶。然而，VHL病中肿瘤发生的确切机制仍未完全了解，关于生物标志物和靶向治疗的知识也很匮乏。
