A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab

Madelyn Espinosa-Cotton, Elana J. Fertig, Laura P. Stabile, Autumn Gaither-Davis, Julie E. Bauman, Sandra Schmitz, Katherine N. Gibson-Corley, Yinwen Cheng, Isaac J. Jensen, Vladimir P. Badovinac, Douglas Laux, Andrean L. Simons

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: The epidermal growth factor receptor (EGFR) monoclonal IgG1 antibody cetuximab is approved for first-line treatment of recurrent and metastatic (R/M) HNSCC as a part of the standard of care EXTREME regimen (platinum/5-fluorouracil/cetuximab). This regimen has relatively high response and disease control rates but is generally not curative and many patients will experience recurrent disease and/or metastasis. Therefore, there is a great need to identify predictive biomarkers for recurrence and disease progression in cetuximab-treated HNSCC patients to facilitate patient management and allow for treatment modification. The goal of this work is to assess the potential of activating interleukin-1 (IL-1) ligands (IL-1 alpha [IL-1α], IL-1 beta [IL-1β]) as predictive biomarkers of survival outcomes in HNSCC patients treated with cetuximab-based chemotherapy. Methods: Baseline gene, serum and tumor expression of interleukin-1 (IL-1) ligands were analyzed from The Cancer Genome Atlas (TCGA) database or clinical trials of cetuximab-based therapies and interrogated for associations with clinical outcome data. Results: High tumor gene expression of IL-1β was associated with a more favorable overall survival in cetuximab-treated HNSCC patients but not in non-cetuximab-treated patients. In HNSCC patients treated with cetuximab-based chemotherapy, higher gene and circulating levels of IL-1α and IL-1β were correlated with a more favorable progression free survival compared to patients with low or undetectable levels of IL-1 ligands. Conclusions: These findings suggest that IL-1 ligands may function as predictive biomarkers for tumor response to cetuximab-based chemotherapy in HNSCC patients and warrants further investigation and validation in larger clinical studies.

Original languageEnglish (US)
Article number14
JournalBiomarker Research
Volume7
Issue number1
DOIs
StatePublished - Jul 16 2019
Externally publishedYes

Keywords

  • Biomarker
  • Cetuximab
  • Head and neck squamous cell carcinoma (HNSCC)
  • Interleukin-1 (IL-1)

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Biochemistry, medical

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