PMID- 33419802
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20211204
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 41
IP  - 1
DP  - 2021 Jan
TI  - Nelfinavir Inhibits the Growth of Small-cell Lung Cancer Cells and 
      Patient-derived Xenograft Tumors.
PG  - 91-99
LID - 10.21873/anticanres.14754 [doi]
AB  - BACKGROUND/AIM: Small-cell lung cancer (SCLC) is aggressive and confers poor 
      prognosis. Although SCLC shows more response to chemotherapy than other types of 
      lung cancer, it is difficult to cure because of its frequent recurrence. New 
      drugs and molecular targets need to be identified. MATERIALS AND METHODS: We 
      investigated the effect of nelfinavir, an HIV protease inhibitor, on SCLC cells 
      and in preclinical treatment studies using SCLC patient-derived xenograft (PDX) 
      mouse models. RESULTS: Nelfinavir inhibited SCLC cell proliferation and induced 
      cell death in vitro, which was caused by induction of the unfolded protein 
      response (UPR), inhibition of mammalian/mechanistic target of rapamycin (mTOR) 
      activation, and reduction in the expression of SCLC-related molecules such as 
      achaete-scute homolog 1 (ASCL1). In vivo, nelfinavir inhibited the growth of SCLC 
      PDX tumors, which correlated with the induction of UPR and reduced expression of 
      ASCL1. CONCLUSION: Nelfinavir is highly effective in SCLC in vitro and in vivo, 
      suggesting possible incorporation of nelfinavir into clinical trials for patients 
      with SCLC.
CI  - Copyright(c) 2021, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Kawabata, Shigeru
AU  - Kawabata S
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      MD, U.S.A. pa1030@osaka-med.ac.jp.
FAU - Connis, Nick
AU  - Connis N
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      MD, U.S.A.
FAU - Gills, Joell J
AU  - Gills JJ
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      MD, U.S.A.
FAU - Hann, Christine L
AU  - Hann CL
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      MD, U.S.A.
FAU - Dennis, Phillip A
AU  - Dennis PA
AD  - Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, 
      MD, U.S.A.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - HO3OGH5D7I (Nelfinavir)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Biomarkers
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - *Drug Repositioning
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/drug therapy/metabolism/pathology
MH  - Mice
MH  - Nelfinavir/*pharmacology/therapeutic use
MH  - Small Cell Lung Carcinoma/drug therapy/metabolism/pathology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Unfolded Protein Response/drug effects
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Small-cell lung cancer
OT  - nelfinavir
OT  - patient-derived xenograft tumors
EDAT- 2021/01/10 06:00
MHDA- 2021/01/26 06:00
CRDT- 2021/01/09 05:30
PHST- 2020/10/30 00:00 [received]
PHST- 2020/11/23 00:00 [accepted]
PHST- 2021/01/09 05:30 [entrez]
PHST- 2021/01/10 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
AID - 41/1/91 [pii]
AID - 10.21873/anticanres.14754 [doi]
PST - ppublish
SO  - Anticancer Res. 2021 Jan;41(1):91-99. doi: 10.21873/anticanres.14754.