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01-12-2019 | Lung Cancer | PRECLINICAL STUDIES

A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer

Authors: Xiaoli Liu, Wei Wang, Yanping Yin, Ming Li, Hong Li, Hang Xiang, Ao Xu, Xiaodong Mei, Bo Hong, Wenchu Lin

Published in: Investigational New Drugs | Issue 6/2019

Summary

Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.

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Title: A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer
Authors: Xiaoli Liu
Wei Wang
Yanping Yin
Ming Li
Hong Li
Hang Xiang
Ao Xu
Xiaodong Mei
Bo Hong
Wenchu Lin
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Lung Cancer
Lung Cancer
SCLC
Cytostatic Therapy
Auranofin
Lung Cancer
SCLC
Published in: Investigational New Drugs / Issue 6/2019
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00750-2

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