A blood biomarker for monitoring response to anti-EGFR therapy
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A blood biomarker for monitoring response to anti-EGFR therapy. / Hughes, Nicholas P; Xu, Lingyun; Nielsen, Carsten H; Chang, Edwin; Hori, Sharon S; Natarajan, Arutselvan; Lee, Samantha; Kjær, Andreas; Kani, Kian; Wang, Shan X; Mallick, Parag; Gambhir, Sanjiv Sam.
In: Cancer Biomarkers, Vol. 22, No. 2, 2018, p. 333-344.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 22
SP - 333
EP - 344
JO - Cancer Biomarkers
JF - Cancer Biomarkers
SN - 1574-0153
IS - 2
ER -
ID: 221827195