PMID- 32988886
OWN - NLM
STAT- MEDLINE
DCOM- 20201007
LR  - 20211204
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 40
IP  - 10
DP  - 2020 Oct
TI  - FGF Expression in HPV16-positive and -negative SCC After Treatment With 
      Small-molecule Tyrosine Kinase Inhibitors and Everolimus.
PG  - 5621-5630
LID - 10.21873/anticanres.14575 [doi]
AB  - BACKGROUND: Targeted therapies in the treatment of head and neck squamous cell 
      carcinoma (HNSCC) are subject to extensive research. Different mutations of genes 
      belonging to the fibroblast growth factor (FGF) family have been detected in 
      HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment 
      with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of 
      mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus 
      (HPV)-positive and -negative SCC lines. MATERIALS AND METHODS: Cells of two human 
      HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) 
      were incubated with 20 mumol/l of erlotinib, gefitinib, nilotinib, dasatinib, or 
      everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay 
      and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked 
      immunosorbent assay. For statistical analysis, the results were compared with 
      those for untreated HPV-negative SCC cells. RESULTS: FGF1 and FGF2 were detected 
      in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) 
      FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time 
      points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and 
      FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was 
      stronger in the HPV-positive cell line. CONCLUSION: Alterations in FGF signalling 
      are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our 
      results show that the expression of FGF1 and -2 can be influenced effectively by 
      small-molecule TKIs and everolimus. Based on our data, future research should 
      include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs 
      in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.
CI  - Copyright(c) 2020, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Huber, Lena
AU  - Huber L
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 
      lena.huber@umm.de.
FAU - Birk, Richard
AU  - Birk R
AD  - Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital 
      Marburg, University of Marburg, Marburg, Germany.
FAU - Knuettel, Manuel
AU  - Knuettel M
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Rotter, Nicole
AU  - Rotter N
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Aderhold, Christoph
AU  - Aderhold C
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Scherl, Claudia
AU  - Scherl C
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Lammert, Anne
AU  - Lammert A
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Jungbauer, Frederic
AU  - Jungbauer F
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
FAU - Kramer, Benedikt
AU  - Kramer B
AD  - Department of Otorhinolaryngology Head and Neck Surgery, University Hospital 
      Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Protein Kinase Inhibitors)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RBZ1571X5H (Dasatinib)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Cell Line, Tumor
MH  - Dasatinib/pharmacology
MH  - Erlotinib Hydrochloride/pharmacology
MH  - Everolimus/*pharmacology
MH  - Fibroblast Growth Factors/antagonists & inhibitors/*genetics
MH  - Gefitinib/pharmacology
MH  - Human papillomavirus 16/drug effects/pathogenicity
MH  - Humans
MH  - Papillomaviridae/drug effects/pathogenicity
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Squamous Cell Carcinoma of Head and Neck/*drug 
      therapy/genetics/pathology/virology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics
OTO - NOTNLM
OT  - FGF
OT  - Fibroblast growth factor
OT  - HNSCC
OT  - HPV
OT  - everolimus
OT  - head and neck squamous cell carcinoma
OT  - mTOR inhibitors
OT  - tyrosine kinase inhibitors
EDAT- 2020/09/30 06:00
MHDA- 2020/10/08 06:00
CRDT- 2020/09/29 05:31
PHST- 2020/07/27 00:00 [received]
PHST- 2020/08/13 00:00 [revised]
PHST- 2020/08/25 00:00 [accepted]
PHST- 2020/09/29 05:31 [entrez]
PHST- 2020/09/30 06:00 [pubmed]
PHST- 2020/10/08 06:00 [medline]
AID - 40/10/5621 [pii]
AID - 10.21873/anticanres.14575 [doi]
PST - ppublish
SO  - Anticancer Res. 2020 Oct;40(10):5621-5630. doi: 10.21873/anticanres.14575.