Specific demonstration of drug-induced tumour cell apoptosis in human xenografts models using a plasma biomarker.
Olofsson, M Hägg Cummings, Jeffrey Fayad, W Brnjic, S Herrmann, R Berndtsson, M Hodgkinson, Cassandra L Dean, Emma J Odedra, Rajesh Wilkinson, Robert W
Olofsson, M Hägg
Cummings, Jeffrey
Fayad, W
Brnjic, S
Herrmann, R
Berndtsson, M
Hodgkinson, Cassandra L
Dean, Emma J
Odedra, Rajesh
Wilkinson, Robert W
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Abstract
Pharmacodynamic (PD) assays should be used before advancing new drugs to clinical trials. Most PD assays measure the response to drugs in tissue, a procedure which requires tissue biopsies. The M30-Apoptosense ELISA is a PD biomarker assay for the quantitative determination of caspase-cleaved cytokeratin 18 (CK18) released from apoptotic carcinoma cells into blood. We here demonstrate that whereas the M30-Apoptosense ELISA assay detects human caspase-cleaved CK18, the mouse and rat CK18 caspase cleavage products are detected with low affinity. The M30-Apoptosense ELISA therefore facilitates the determination of drug-induced apoptosis in human tumour xenografts in rodents using plasma samples, largely independently from host toxicity. Increases of caspase-cleaved CK18 were observed in plasma from different carcinoma xenograft models in response to anticancer drugs. The appearance caspase-cleaved CK18 in plasma was found to reflect formation of the caspase-cleaved epitope in FaDu head-neck carcinomas and in cultured cells. The M30-Apoptosense assay allows determination of tumour response in blood from xenograft models and from patients, providing a powerful tool for translational studies of anticancer drugs.
Description
Date
2009
Publisher
Keywords
Cell Line Tumours
Colonic Cancer
Head and Neck Cancer
Experimental Cancer
Biological Tumour Markers
Colonic Cancer
Head and Neck Cancer
Experimental Cancer
Biological Tumour Markers
Type
Article
Citation
Specific demonstration of drug-induced tumour cell apoptosis in human xenografts models using a plasma biomarker. 2009, 5 (3):117-25 Cancer Biomark