Elsevier

Papillomavirus Research

Volume 8, December 2019, 100181
Papillomavirus Research

High-throughput screening identifies candidate drugs for the treatment of recurrent respiratory papillomatosis

https://doi.org/10.1016/j.pvr.2019.100181Get rights and content
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Abstract

Recurrent respiratory papillomatosis (RRP) is a benign neoplasm of the larynx caused mainly by human papillomavirus type 6 or 11 and its standard treatment involves repeated surgical debulking of the laryngeal tumors. However, significant morbidity and occasional mortality due to multiple recurrences occur. Conditional reprogramming (CR) was used to establish a HPV-6 positive culture from an RRP patient, named GUMC-403. High-throughput screening was performed at the National Center for Advanced Technology (NCATS) to identify potential drugs to treat this rare but morbid disease. GUMC-403 cells were screened against the NPC library of >2800 approved drugs and the MIPE library of >1900 investigational drugs to identify new uses for FDA-approved drugs or drugs that have undergone significant research and development. From the two libraries, we identified a total of 13 drugs that induced significant cytotoxicity in RRP cells at IC50 values that were clinically achievable. We validated the efficacy of the drugs in vitro using CR 2D and 3D models and further refined our list of drugs to panobinostat, dinaciclib and forskolin as potential therapies for RRP patients.

Keywords

Primary cell culture
Recurrent respiratory papillomatosis
High-throughput screening
Panobinostat
Dinaciclib
Forskolin
Drug sensitivity
Repurposing

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