PMID- 32446385
OWN - NLM
STAT- MEDLINE
DCOM- 20201221
LR  - 20201221
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 527
IP  - 1
DP  - 2020 Jun 18
TI  - Inhibition of JAK1/2 can overcome EGFR-TKI resistance in human NSCLC.
PG  - 305-310
LID - S0006-291X(20)30818-4 [pii]
LID - 10.1016/j.bbrc.2020.04.095 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Kim, Dong Min
AU  - Kim DM
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Convergence Medicine, Asan Medical Center University of Ulsan 
      College of Medicine, Seoul, Republic Korea.
FAU - Kim, Mi Jin
AU  - Kim MJ
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Convergence Medicine, Asan Medical Center University of Ulsan 
      College of Medicine, Seoul, Republic Korea.
FAU - Moon, Jai-Hee
AU  - Moon JH
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Eun Young
AU  - Lee EY
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Hong, Jun Ki
AU  - Hong JK
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Seul
AU  - Lee S
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Koh, Dong-In
AU  - Koh DI
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Ryu, Yae Seong
AU  - Ryu YS
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Seung Mi
AU  - Kim SM
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Jung, Soo-A
AU  - Jung SA
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Shin, Jae-Sik
AU  - Shin JS
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Kim, Joseph
AU  - Kim J
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Park, Yoon Sun
AU  - Park YS
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Hong, Seung-Woo
AU  - Hong SW
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Lee, So Hee
AU  - Lee SH
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Jung, Joonyee
AU  - Jung J
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Park, Sang Soo
AU  - Park SS
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Do Yeon
AU  - Kim DY
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Eun Ho
AU  - Kim EH
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Jeong, Hong-Rae
AU  - Jeong HR
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Medical Science, Asan Medical Institute of Convergence Science and 
      Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 
      Republic of Korea.
FAU - Gong, Ji Hee
AU  - Gong JH
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Kim, Jieun
AU  - Kim J
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
FAU - Chan Kim, Seung
AU  - Chan Kim S
AD  - CJ HealthCare R&D Center, Icheon-si, Gyeonggi-do, Republic of Korea.
FAU - Yu, Ha Na
AU  - Yu HN
AD  - CJ HealthCare R&D Center, Icheon-si, Gyeonggi-do, Republic of Korea.
FAU - Ki, So Young
AU  - Ki SY
AD  - CJ HealthCare R&D Center, Icheon-si, Gyeonggi-do, Republic of Korea.
FAU - Kim, Tae Won
AU  - Kim TW
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Oncology, Asan Medical Center University of Ulsan College of 
      Medicine, Seoul, Republic Korea. Electronic address: twkimmd@amc.seoul.kr.
FAU - Jin, Dong-Hoon
AU  - Jin DH
AD  - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea; 
      Department of Convergence Medicine, Asan Medical Center University of Ulsan 
      College of Medicine, Seoul, Republic Korea. Electronic address: 
      inno183@amc.seoul.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200511
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/pathology
MH  - Cell Death/drug effects
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Drug Screening Assays, Antitumor
MH  - ErbB Receptors/antagonists & inhibitors/genetics/metabolism
MH  - Erlotinib Hydrochloride/chemistry/*pharmacology
MH  - Female
MH  - Humans
MH  - Janus Kinase 1/*antagonists & inhibitors/metabolism
MH  - Lung Neoplasms/*drug therapy/metabolism/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Molecular Structure
MH  - Mutation
MH  - Neoplasms, Experimental/drug therapy/metabolism/pathology
MH  - Protein Kinase Inhibitors/chemistry/*pharmacology
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - CJ14939
OT  - EGFR inhibitor
OT  - Erlotinib
OT  - JAK inhibitor
OT  - NSCLC
OT  - Resistance
COIS- Declaration of competing interest The authors declare no competing financial 
      interest.
EDAT- 2020/05/25 06:00
MHDA- 2020/12/22 06:00
CRDT- 2020/05/25 06:00
PHST- 2020/04/05 00:00 [received]
PHST- 2020/04/18 00:00 [accepted]
PHST- 2020/05/25 06:00 [entrez]
PHST- 2020/05/25 06:00 [pubmed]
PHST- 2020/12/22 06:00 [medline]
AID - S0006-291X(20)30818-4 [pii]
AID - 10.1016/j.bbrc.2020.04.095 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Jun 18;527(1):305-310. doi: 
      10.1016/j.bbrc.2020.04.095. Epub 2020 May 11.