A blood biomarker for monitoring response to anti-EGFR therapy

Article type: Research Article

Authors: Hughes, Nicholas P.^{a; 1} | Xu, Lingyun^{a; b; 1} | Nielsen, Carsten H.^{a; c; d; 1} | Chang, Edwin^{a; b; 1} | Hori, Sharon S.^{a; b} | Natarajan, Arutselvan^{a; b} | Lee, Samantha^b | Kjær, Andreas^{c; d} | Kani, Kian^e | Wang, Shan X.^{f; g} | Mallick, Parag^{a; b} | Gambhir, Sanjiv Sam^{a; b; f; g; *}

Affiliations: [a] Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA | [b] Canary Center at Stanford for Cancer Early Detection, Palo Alto, CA, USA | [c] Department of Clinical Physiology, Nuclear Medicine and PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark | [d] Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark | [e] Lawrence J. Ellison Institute of Transformative Medicine, University of Southern California, Los Angeles, CA, USA | [f] Department of Bioengineering, Stanford University, Stanford, CA, USA | [g] Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA

Correspondence: [*] Corresponding author: Sanjiv Sam Gambhir, Department of Radiology, Stanford University, James H. Clark Center, 318 Campus Drive, E153, Stanford, CA 94305, USA. Tel.: +1 650 725 6175; Fax: +1 650 724 4948;

Note: [1] These authors contributed equally to this work.

Abstract: BACKGROUND AND OBJECTIVE: To monitor therapies targeted to epidermal growth factor receptors (EGFR) in non-small cell lung cancer (NSCLC), we investigated Peroxiredoxin 6 (PRDX6) as a biomarker of response to anti-EGFR agents. METHODS: We studied cells that are sensitive (H3255, HCC827) or resistant (H1975, H460) to gefitinib. PRDX6 was examined with either gefitinib or vehicle treatment using enzyme-linked immunosorbent assays. We created xenograft models from one sensitive (HCC827) and one resistant cell line (H1975) and monitored serum PRDX6 levels during treatment. RESULTS: PRDX6 levels in cell media from sensitive cell lines increased significantly after gefitinib treatment vs. vehicle, whereas there was no significant difference for resistant lines. PRDX6 accumulation over time correlated positively with gefitinib sensitivity. Serum PRDX6 levels in gefitinib-sensitive xenograft models increased markedly during the first 24 hours of treatment and then decreased dramatically during the following 48 hours. Differences in serum PRDX6 levels between vehicle and gefitinib-treated animals could not be explained by differences in tumor burden. CONCLUSIONS: Our results show that changes in serum PRDX6 during the course of gefitinib treatment of xenograft models provide insight into tumor response and such an approach offers several advantages over imaging-based strategies for monitoring response to anti-EGFR agents.

Keywords: Serum biomarkers, gefitinib, EGFR, NSCLC, proteomics, ELISA

DOI: 10.3233/CBM-171149

Journal: Cancer Biomarkers, vol. 22, no. 2, pp. 333-344, 2018