Comet assay measures of DNA damage as biomarkers of irinotecan response in colorectal cancer in vitro and in vivo

摘要: The use of irinotecan to treat metastatic colorectal cancer (CRC) is limited by unpredictable response and variable toxicity; however, no reliable clinical biomarkers are available. Here, we report a study ascertain whether irinotecan-induced DNA damage measures suitable/superior effect. CRC-cell lines (HCT-116 HT-29) were treated in vitro with peripheral blood lymphocytes (PBL) isolated from patients before after receiving irinotecan-based chemotherapy. Levels in vitro-, in vivo-, ex vivo-induced measured using the Comet assay; correlations between levels cell survival follow-up data investigated. Irinotecan-induced was detectable in both CRC cell-lines in vitro, higher immediate residual noted for more sensitive HT-29 cells. not detected in vivo, but measurable PBLs upon mitogenic stimulation prior ex vivo SN-38 treatment. Results showed that, following corrections experimental error, those whose demonstrated 10 h exposure had significantly longer times progression than lower (median 291 vs. 173 days, P = 0.014). To conclude, initial correlated greater kill better response. Consequently, may represent superior effect compared often-studied genetic assays differential drug metabolism.