Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Eur J Cancer. 2013 Jul;49(11):2512-21. doi: 10.1016/j.ejca.2013.03.011. Epub 2013 Apr 10.

A novel serum protein signature associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors in head and neck squamous cell carcinoma.

Author information

  • 1Tumour Biology & Metastasis Team, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  • 2Pathology and Oncology Laboratory, IdiPAZ, Hospital La Paz, Madrid 28046, Spain.
  • 3Tumour Biology & Metastasis Team, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK; Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  • 4Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
  • 5The Head and Neck Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
  • 6The Head and Neck Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK; Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
  • 7Tumour Biology & Metastasis Team, Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK; Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. Electronic address: sue.eccles@icr.ac.uk.

Abstract

BACKGROUND:

Acquired resistance to tyrosine kinase inhibitors (TKIs) is becoming a major challenge in the treatment of many cancers. Epidermal growth factor receptor (EGFR) is overexpressed in squamous carcinomas, notably those of the head and neck (HNSCC), and can be targeted with several TKIs. We aimed to identify soluble proteins suitable for development as markers of EGFR TKI resistance in cancer patients to aid in early and minimally invasive assessment of therapeutic responses.

METHODS:

Resistant HNSCC cell lines were generated by exposure to an EGFR TKI, gefitinib, in vitro. Cell lines were characterised for their biological behaviour in vitro (using growth inhibition assays, flow cytometry, western blots, antibody arrays and/or immunoassays) and in vivo (using subcutaneous tumour xenografts). Sera from EGFR-treated and -untreated HNSCC patients were analysed by immunoassay.

RESULTS:

Two independent sublines of CAL 27 and a PJ34 subline with acquired resistance to EGFR TKIs (gefitinib, erlotinib and afatinib) were developed. Resistant cells grew as highly aggressive xenografts leading to reduced host survival rates compared with EGFR-TKI sensitive cells. This suggested a link between resistance in vitro and poor prognosis in vivo. A significant upregulation of proteins linked to tumour angiogenesis and invasion was identified in resistant cells. This 'resistance-associated protein signature' (RAPS) was detected in the sera of a small cohort of HNSCC patients and was associated with reduced survival.

CONCLUSION:

We have identified a protein signature associated with EGFR-TKI resistance that may also be linked to poor prognosis and warrants further investigation as a potential clinical biomarker.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID:
23582742
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk