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. 2020 Jun 18;527(1):305-310.
doi: 10.1016/j.bbrc.2020.04.095. Epub 2020 May 11.

Inhibition of JAK1/2 can overcome EGFR-TKI resistance in human NSCLC

Dong Min Kim  1 , Mi Jin Kim  1 , Jai-Hee Moon  2 , Eun Young Lee  2 , Jun Ki Hong  2 , Seul Lee  2 , Dong-In Koh  3 , Yae Seong Ryu  2 , Seung Mi Kim  3 , Soo-A Jung  2 , Jae-Sik Shin  3 , Joseph Kim  2 , Yoon Sun Park  2 , Seung-Woo Hong  3 , So Hee Lee  3 , Joonyee Jung  3 , Sang Soo Park  2 , Do Yeon Kim  2 , Eun Ho Kim  2 , Hong-Rae Jeong  2 , Ji Hee Gong  3 , Jieun Kim  3 , Seung Chan Kim  4 , Ha Na Yu  4 , So Young Ki  4 , Tae Won Kim  5 , Dong-Hoon Jin  6
Affiliations

Inhibition of JAK1/2 can overcome EGFR-TKI resistance in human NSCLC

Dong Min Kim et al. Biochem Biophys Res Commun. .

Abstract

Non-small lung cancer (NSCLC) is the most common cancer in the world. The epidermal growth factor receptor (EGFR) gene is mutated in approximately 10% of lung cancer cases in the US and 50% of lung cancer in Asia. The representative target therapeutic agent, erlotinib (EGFR tyrosine kinase inhibitor; EGFR TKI), is effective in inactivating EGFR in lung cancer patients. However, approximately 50-60% of patients are resistant to EGFR TKI. These populations are associated with the EGFR mutation. To overcome resistance to EGFR TKI, we discovered a JAK1 inhibitor, CJ14939. We investigated the efficacy of CJ14939 in human NSCLC cell lines in vitro and in vivo. Our results showed that CJ14939 induced the inhibition of cell growth. Moreover, we demonstrated that combination treatment with erlotinib and CJ14939 induced cell death in vitro and inhibited tumor growth in vivo. In addition, we confirmed the suppression of phosphorylated EGFR, JAK1, and Stat3 expression in erlotinib and CJ14939-treated human NSCLC cell lines. Our results provide evidence that JAK inhibition overcomes resistance to EGFR TKI in human NSCLCs.

Keywords: CJ14939; EGFR inhibitor; Erlotinib; JAK inhibitor; NSCLC; Resistance.

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Conflict of interest statement

Declaration of competing interest The authors declare no competing financial interest.

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