Proteostasis Modulation in Germline Missense von Hippel Lindau Disease.

ABSTRACT:

Purpose

Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation and/or progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in preclinical models. We asked whether short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in patients with germline missense VHL.

Patients and methods

We administered oral vorinostat to 7 subjects (ages 46.0 ± 14.5 years) and then removed symptomatic hemangioblastomas surgically (ClinicalTrials.gov identifier NCT02108002).

Results

Vorinostat was tolerated without serious adverse events by all patients. pVHL expression was elevated in neoplastic stromal cells compared with untreat

SUBMITTER: Chittiboina P 

PROVIDER: S-EPMC10330138 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature