A blood biomarker for monitoring response to anti-EGFR therapy

Research output: Contribution to journalJournal articleResearchpeer-review

Nicholas P Hughes, Lingyun Xu, Carsten H Nielsen, Edwin Chang, Sharon S Hori, Arutselvan Natarajan, Samantha Lee, Andreas Kjær, Kian Kani, Shan X Wang, Parag Mallick, Sanjiv Sam Gambhir

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.

Original languageEnglish
JournalCancer Biomarkers
Volume22
Issue number2
Pages (from-to)333-344
Number of pages12
ISSN1574-0153
DOIs
Publication statusPublished - 2018

    Research areas

  • Animals, Antineoplastic Agents/pharmacology, Biomarkers, Carcinoma, Non-Small-Cell Lung/blood, Cell Line, Tumor, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, ErbB Receptors/antagonists & inhibitors, Female, Gefitinib, Humans, Lung Neoplasms/blood, Mice, Peroxiredoxin VI/blood, Protein Kinase Inhibitors/pharmacology, Quinazolines/pharmacology, Treatment Outcome, Xenograft Model Antitumor Assays

ID: 221827195