Proteasome inhibition as a therapeutic approach in atypical teratoid/rhabdoid tumors.

ABSTRACT:

Background

Atypical teratoid/thabdoid tumor (AT/RT) remains a difficult-to-treat tumor with a 5-year overall survival rate of 15%-45%. Proteasome inhibition has recently been opened as an avenue for cancer treatment with the FDA approval of bortezomib (BTZ) in 2003 and carfilzomib (CFZ) in 2012. The aim of this study was to identify and characterize a pre-approved targeted therapy with potential for clinical trials in AT/RT.

Methods

We performed a drug screen using a panel of 134 FDA-approved drugs in 3 AT/RT cell lines. Follow-on in vitro studies used 6 cell lines and patient-derived short-term cultures to characterize selected drug interactions with AT/RT. In vivo efficacy was evaluated using patient derived xenografts in an intracranial murine model.

Results

BTZ an

SUBMITTER: Morin A 

PROVIDER: S-EPMC7236404 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature