title: FS-93, an Hsp90 inhibitor, induces G2/M arrest and apoptosis via the degradation of client proteins in oncogene addicted and derived resistant cancer cells.
abstract: Inhibition of heat shock protein 90 (Hsp90) abrogates signaling of multiple aberrantly activated oncogenic proteins simultaneously, particularly mutated or amplified kinases, which provides an attractive approach for cancer treatment. Here, we described that FS-93, a potent Hsp90 inhibitor, impacted the survival of several types of oncogene addicted cancer cells through inducing G2/M arrest and apoptosis. Mechanistically, FS-93 treatment triggered the degradation of key client proteins such as HER2, EML4-ALK and c-Met and thereby abolished their downstream signaling pathways. Importantly, FS-93 alone circumvented MET amplification contributed acquired resistance to EGFR inhibition. Our study implicates that targeting Hsp90 is a promising alternative therapeutic tactic in oncogene addicted and derived resistant cancer cells.
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Shandong, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Shen
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Synthetic Organic and Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Danqi
authors.initials: D
authors.lastname: Chen
authors.affiliation: Synthetic Organic and Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiong
authors.affiliation: Synthetic Organic and Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jingkang
authors.initials: J
authors.lastname: Shen
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
keywords: G2/M arrest; apoptosis; hsp90; oncogene addiction; resistance