Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action

Curr Opin Urol. 2022 Jan 1;32(1):31-39. doi: 10.1097/MOU.0000000000000950.

Abstract

Purpose of review: While the molecular and genetic bases of Von Hippel-Lindau (VHL) disease have been extensively investigated, limited evidence is available to guide diagnosis, local or systemic therapy, and follow-up. The aim of the current review is to summarize the ongoing trials both in preclinical and clinical setting regarding VHL disease management.

Recent findings: Although genotype/phenotype correlations have been described, there is considerable inter and intra-familiar heterogeneity in VHL disease. Genetic anticipation has been reported in VHL disease. From a clinical point of view, expert-opinion-based protocols suggest testing those patients with any blood relative of an individual diagnosed with VHL disease, those with at least 1 or more suggestive neoplasms or patients presenting with clear cell renal cell carcinoma (ccRCC) diagnosed at a less than 40 years old, and/or multiple ccRCC. Clinical research is focused on safety and efficacy of systemic agents for patients with VHL-related ccRCC, with the aim to possibly preserve kidney function and improve patient survival.

Summary: To date, preclinical and clinical research on the topic is scarce and clinical guidelines are not supported by strong validation studies.

Trial registration: ClinicalTrials.gov NCT01266070 NCT03108066 NCT03907657 NCT03749980.

Publication types

  • Review

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / therapy
  • Female
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / therapy
  • Male
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics
  • von Hippel-Lindau Disease* / complications
  • von Hippel-Lindau Disease* / genetics
  • von Hippel-Lindau Disease* / therapy

Substances

  • Von Hippel-Lindau Tumor Suppressor Protein

Associated data

  • ClinicalTrials.gov/NCT01266070
  • ClinicalTrials.gov/NCT03108066
  • ClinicalTrials.gov/NCT03907657
  • ClinicalTrials.gov/NCT03749980