LB19
Detection of therapy-induced tumour death biomarkers in patient serum samples
Frank Neumann1, Klaus Mross2, Marc Azemar2, Vittorio Zirol2, Ulrich Massing2, Clemens Unger2, Bernd Hildenbrand2
1BIOAXXESS Technology, Malvern, UK, 2Tumor Biology Center at the Albert-Ludwigs-University, Freiburg, Germany
Introduction
M30-Apoptosense and M65 are validated; CE-marked enzyme-linked immunosorbent assays that detect circulating cytokeratin 18 fragments released during caspase-dependent (apoptotic) or total cell death, respectively, and have shown potential as biomarkers in epithelial cancers. We present clinical data of the M30 and M65 serum ELISAs as biomarkers of drug-induced tumor cell death and disease activity.
Objective
To investigate, whether the caspase-cleaved neoepitope of cytokeratin 18 fragments (CK18F/M30) and/or total CK18(M65) might be a serum marker for drug-induced carcinoma cell death and/or tissue toxicity. To define the optimal time window for serum sampling for future cell death biomarker analysis.
To investigate any contribution of the presence of liver metastases and liver injury prior treatment on CK18 signal strength and pattern.
Method
M30 and M65 were measured in serum samples from 11 patients suffering from carcinomas of the breast, ovaries, oesophagus and larynx, were taken shortly before, during and after treatment with Paclitaxel as part of a PD clinical study.
Results
The majority of patients with an increase in total CK18 (M65) serum levels upon treatment showed a concomitant and comparable increase of the apoptotic M30 (caspase-cleaved CK18) serum biomarker. No effect of the presence of liver metastases or elevated liver enzymes on baseline or the extent of increases in M30 or M65 (total CK18) serum levels.
Conclusion
Monitoring of serum CK18 levels by ELISA prior, during and after chemotherapy therapy may provide a simple method for quantitative assessment of carcinoma-associated anti-tumour activity in different tumour types.
