A blood biomarker for monitoring response to anti-EGFR therapy

TY - JOUR

T1 - A blood biomarker for monitoring response to anti-EGFR therapy

AU - Hughes, Nicholas P

AU - Xu, Lingyun

AU - Nielsen, Carsten H

AU - Chang, Edwin

AU - Hori, Sharon S

AU - Natarajan, Arutselvan

AU - Lee, Samantha

AU - Kjær, Andreas

AU - Kani, Kian

AU - Wang, Shan X

AU - Mallick, Parag

AU - Gambhir, Sanjiv Sam

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents/pharmacology

KW - Biomarkers

KW - Carcinoma, Non-Small-Cell Lung/blood

KW - Cell Line, Tumor

KW - Disease Models, Animal

KW - Enzyme-Linked Immunosorbent Assay

KW - ErbB Receptors/antagonists & inhibitors

KW - Female

KW - Gefitinib

KW - Humans

KW - Lung Neoplasms/blood

KW - Mice

KW - Peroxiredoxin VI/blood

KW - Protein Kinase Inhibitors/pharmacology

KW - Quinazolines/pharmacology

KW - Treatment Outcome

KW - Xenograft Model Antitumor Assays

U2 - 10.3233/CBM-171149

DO - 10.3233/CBM-171149

M3 - Journal article

C2 - 29689709

SN - 1574-0153

VL - 22

SP - 333

EP - 344

JO - Cancer Biomarkers

JF - Cancer Biomarkers

IS - 2

ER -