Systemic Therapy Development in Von Hippel–Lindau Disease: An Outsized Contribution from an Orphan Disease

SIMPLE SUMMARY: This review highlights the development of systemic anti-neoplastic therapies for the treatment of patients with von Hippel–Lindau disease, culminating with the recent approval of the first systemic agent for this disease. ABSTRACT: Over the last several decades, an improved understanding of von Hippel–Lindau disease and its underlying biology has informed the successful development of numerous anti-cancer agents, particularly for the treatment of advanced renal cell carcinoma. Most recently, this has culminated in the first regulatory approval for a systemic therapy for VHL disease-associated neoplasms. This review will trace the clinical development of systemic therapies for VHL disease and additionally highlight anticipated challenges and opportunities for future VHL systemic therapy.