Abstract:
Objective:To explore the possibility of monitoring tumor cell death in real-time for early determination of re -sponse to chemotherapy. Methods:Intracellular macromolecules are released from dying tumor cells and can subsequently be detected in patient blood. The M30antibody was used to detect the caspase-degraded product of the cytoskeletal pro -tein CK 18denoted as CK 18-Asp396 during apoptosis of epithelial cells, and the M65antibody was used to detect all of the products of CK 18during apoptosis and necrosis. The change in CK18-Asp396 and total soluble CK18levels could be used to monitor the apoptosis and death of tumor cells. Sera from 30patients with breast cancer were collected at24-48hours before and after the 1st cycle of chemotherapy and the content of CK18-Asp396 and total soluble CK18was quantitatively examined with ELISA assays. Correlations between the change in CK18and efficacy were determined by χ2 test. Results: Of the 30patients, there were 2 patients with stageⅡB, 11with stage ⅢA, 1 with stage ⅢB, 2 with stage ⅢC and 14with stage Ⅳdisease. All30patients received a combined chemotherapy regimen based on anthracyclines and/or taxans. After 4 cycles, RECIST criteria were used to evaluate the response. Three patients had a complete response, 19patients had partial response, 7 had stable disease and 1 had progressive disease. The response rate was 73.3 % (22/30). All of the 19 patients who displayed changes in caspase-cleaved CK 18>20% and/or change in total soluble CK18>30% responded. Among the other 11patients, 3 patients had PR, 7 had SD and 1 had PD (χ2= 18.843 , P = 0.001 ). Conclusion:There is a significant relationship of increase in caspase-cleaved CK 18and total soluble CK18 level in serum with overall response to therapy. CK18-Asp396 and total soluble CK18might be used as a novel biomarker for early prediction of response to che-motherapy in patients with breast cancer or other malignant tumors.