Enniatin A inhibits the chaperone Hsp90 and unleashes the immune system against triple-negative breast cancer.

Authors

• Nada H Eisa
• Vincent M Crowley
• Asif Elahi
• Vamsi Krishna Kommalapati
• Michael A Serwetnyk
• Taoufik Llbiyi
• Sumin Lu
• Kashish Kainth
• Yasmeen Jilani
• Daniela Marasco
• Abdeljabar El Andaloussi
• Sukyeong Lee
• Francis T F Tsai
• Paulo C Rodriguez
• David Munn
• Esteban Celis
• Hasan Korkaya
• Abdessamad Debbab
• Brian Blagg
• Ahmed Chadli

Publication/Presentation Date

12-15-2023

Abstract

Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) and less than optimal dosing of these inhibitors limited their clinical efficacy as monotherapies. We discovered that the natural product Enniatin A (EnnA) targets Hsp90 and destabilizes its client oncoproteins without inducing an HSR. EnnA triggers immunogenic cell death in triple-negative breast cancer (TNBC) syngeneic mouse models and exhibits superior antitumor activity compared to Hsp90 N-terminal inhibitors. EnnA reprograms the tumor microenvironment (TME) to promote CD8

Volume

26

Issue

12

First Page

108308

Last Page

108308

ISSN

2589-0042

Published In/Presented At

Eisa, N. H., Crowley, V. M., Elahi, A., Kommalapati, V. K., Serwetnyk, M. A., Llbiyi, T., Lu, S., Kainth, K., Jilani, Y., Marasco, D., El Andaloussi, A., Lee, S., Tsai, F. T. F., Rodriguez, P. C., Munn, D., Celis, E., Korkaya, H., Debbab, A., Blagg, B., & Chadli, A. (2023). Enniatin A inhibits the chaperone Hsp90 and unleashes the immune system against triple-negative breast cancer. iScience, 26(12), 108308. https://doi.org/10.1016/j.isci.2023.108308

Disciplines

Medicine and Health Sciences

PubMedID

38025772

Department(s)

Fellows and Residents

Document Type

Article