PMID- 31536667
OWN - NLM
STAT- MEDLINE
DCOM- 20201030
LR  - 20221202
IS  - 1749-4486 (Electronic)
IS  - 1749-4478 (Linking)
VI  - 44
IP  - 6
DP  - 2019 Nov
TI  - Radioresistant laryngeal cancers upregulate type 1 IGF receptor and exhibit 
      increased cellular dependence on IGF and EGF signalling.
PG  - 1026-1036
LID - 10.1111/coa.13434 [doi]
AB  - OBJECTIVES: Patients failing radiotherapy for laryngeal squamous cell carcinoma 
      (LSCC) often require salvage total laryngectomy which has major functional 
      consequences, highlighting a need for biomarkers of radiotherapy resistance. In 
      other tumour types, radioresistance has been linked to epidermal growth factor 
      receptor (EGFR) and type 1 insulin-like growth factor receptor (IGF-1R). Here, we 
      evaluated IGF-1R and EGFR as predictors and mediators of LSCC radioresistance. 
      DESIGN: We compared IGF-1R and EGFR immunohistochemical scores in patients with 
      LSCC achieving long-term remission post-radiotherapy (n = 23), patients treated 
      with primary laryngectomy (n = 22) or salvage laryngectomy following radiotherapy 
      recurrence (n = 18). To model radioresistance in vitro, two LSCC cell lines 
      underwent clinically relevant irradiation to 55 Gy in 2.75 Gy fractions. RESULTS: 
      Type 1 insulin-like growth factor receptor expression was higher in pre-treatment 
      biopsies of radiotherapy failures compared with those in long-term remission and 
      was upregulated post-radiotherapy. Patients undergoing primary laryngectomy had 
      more advanced T/N stage and greater tumour IGF-1R content than those achieving 
      long-term remission. Pre-treatment EGFR did not associate with radiotherapy 
      outcomes but showed a trend to upregulation post-irradiation. In vitro, 
      radiosensitivity was enhanced by inhibition of EGFR but not IGF. Repeated 
      irradiation upregulated IGF-1R in BICR18 and SQ20B cells and EGFR in SQ20B, and 
      enhanced SQ20B radioresistance. Repeatedly irradiated SQ20B_55 cells were not 
      radiosensitised by inhibition of IGF and/or EGFR, but IGF-1R:EGFR co-inhibition 
      suppressed baseline cell survival more effectively than blockade of either 
      pathway alone, and more effectively than in parental cells. CONCLUSIONS: 
      Radiation upregulates IGF-1R and may enhance IGF/EGFR dependence, suggesting that 
      IGF/EGFR blockade may have activity in LSCCs that recur post-radiotherapy.
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Qureishi, Ali
AU  - Qureishi A
AUID- ORCID: 0000-0001-8654-6888
AD  - Department of Oncology, University of Oxford, Oxford, UK.
AD  - Nuffield Department of Surgery, University of Oxford and Department of Head and 
      Neck Surgery, Oxford University Hospitals NHS Foundation Trust, Churchill 
      Hospital, Oxford, UK.
FAU - Rieunier, Guillaume
AU  - Rieunier G
AD  - Department of Oncology, University of Oxford, Oxford, UK.
FAU - Shah, Ketan A
AU  - Shah KA
AD  - Department of Cellular Pathology, Oxford University Hospitals NHS Foundation 
      Trust, John Radcliffe Hospital, Oxford, UK.
FAU - Aleksic, Tamara
AU  - Aleksic T
AD  - Department of Oncology, University of Oxford, Oxford, UK.
FAU - Winter, Stuart C
AU  - Winter SC
AUID- ORCID: 0000-0002-8152-816X
AD  - Nuffield Department of Surgery, University of Oxford and Department of Head and 
      Neck Surgery, Oxford University Hospitals NHS Foundation Trust, Churchill 
      Hospital, Oxford, UK.
FAU - Moller, Henrik
AU  - Moller H
AD  - School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
FAU - Macaulay, Valentine M
AU  - Macaulay VM
AUID- ORCID: 0000-0001-8659-0192
AD  - Department of Oncology, University of Oxford, Oxford, UK.
AD  - Oxford Cancer and Haematology Centre, Oxford University Hospitals NHS Foundation 
      Trust, Churchill Hospital, Oxford, UK.
LA  - eng
GR  - 27060/CRUK_/Cancer Research UK/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
DEP - 20191004
PL  - England
TA  - Clin Otolaryngol
JT  - Clinical otolaryngology : official journal of ENT-UK ; official journal of 
      Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery
JID - 101247023
RN  - 0 (IGF1R protein, human)
RN  - 0 (Somatomedins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Aged
MH  - Carcinoma, Squamous Cell/metabolism/pathology/*radiotherapy
MH  - Cohort Studies
MH  - Epidermal Growth Factor/*metabolism
MH  - Female
MH  - Humans
MH  - Laryngeal Neoplasms/metabolism/pathology/*radiotherapy
MH  - Laryngectomy
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Radiation Tolerance
MH  - Receptor, IGF Type 1/*metabolism
MH  - Signal Transduction/*physiology
MH  - Somatomedins/*metabolism
OTO - NOTNLM
OT  - afatinib
OT  - epidermal growth factor receptor
OT  - laryngeal squamous cell cancer
OT  - radioresistance
OT  - radiotherapy
OT  - type 1 IGF receptor
OT  - xentuzumab
EDAT- 2019/09/20 06:00
MHDA- 2020/10/31 06:00
CRDT- 2019/09/20 06:00
PHST- 2018/12/21 00:00 [received]
PHST- 2019/08/01 00:00 [revised]
PHST- 2019/09/13 00:00 [accepted]
PHST- 2019/09/20 06:00 [pubmed]
PHST- 2020/10/31 06:00 [medline]
PHST- 2019/09/20 06:00 [entrez]
AID - 10.1111/coa.13434 [doi]
PST - ppublish
SO  - Clin Otolaryngol. 2019 Nov;44(6):1026-1036. doi: 10.1111/coa.13434. Epub 2019 Oct 
      4.