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

Madelyn Espinosa-Cotton, Elana 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 journalArticle

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

Fingerprint

Biomarkers
Interleukin-1
Ligands
Chemotherapy
Genes
Drug Therapy
Tumors
Disease control
Cetuximab
Neoplasms
Interleukin-1alpha
Monoclonal antibodies
Survival
Atlases
Standard of Care
Tumor Biomarkers
Platinum
Interleukin-1beta
Epidermal Growth Factor Receptor
Gene expression

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Espinosa-Cotton, M., Fertig, E., Stabile, L. P., Gaither-Davis, A., Bauman, J. E., Schmitz, S., ... Simons, A. L. (2019). A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab. Biomarker Research, 7(1), [14]. https://doi.org/10.1186/s40364-019-0164-0

A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab. / Espinosa-Cotton, Madelyn; Fertig, Elana; Stabile, Laura P.; Gaither-Davis, Autumn; Bauman, Julie E.; Schmitz, Sandra; Gibson-Corley, Katherine N.; Cheng, Yinwen; Jensen, Isaac J.; Badovinac, Vladimir P.; Laux, Douglas; Simons, Andrean L.

In: Biomarker Research, Vol. 7, No. 1, 14, 16.07.2019.

Research output: Contribution to journalArticle

Espinosa-Cotton, M, Fertig, E, Stabile, LP, Gaither-Davis, A, Bauman, JE, Schmitz, S, Gibson-Corley, KN, Cheng, Y, Jensen, IJ, Badovinac, VP, Laux, D & Simons, AL 2019, 'A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab', Biomarker Research, vol. 7, no. 1, 14. https://doi.org/10.1186/s40364-019-0164-0
Espinosa-Cotton, Madelyn ; Fertig, Elana ; Stabile, Laura P. ; Gaither-Davis, Autumn ; Bauman, Julie E. ; Schmitz, Sandra ; Gibson-Corley, Katherine N. ; Cheng, Yinwen ; Jensen, Isaac J. ; Badovinac, Vladimir P. ; Laux, Douglas ; Simons, Andrean L. / A preliminary analysis of interleukin-1 ligands as potential predictive biomarkers of response to cetuximab. In: Biomarker Research. 2019 ; Vol. 7, No. 1.
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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.",
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AU - Bauman, Julie E.

AU - Schmitz, Sandra

AU - Gibson-Corley, Katherine N.

AU - Cheng, Yinwen

AU - Jensen, Isaac J.

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