TOXI 124 |
| These Pt-containing anticancer drugs cisplatin, carboplatin, and oxaliplatin cause DNA damage leading to cell death, and can also bind to proteins. However, the roles of drug-protein interactions in the drugs' action and toxicity are not well understood. We present here the study of interactions between blood proteins and platinum drugs using nanospray tandem mass spectrometry (nanoESI-MS) and liquid chromatography with inductively coupled plasma mass spectrometry (SELC-ICPMS) techniques. In vitro studies show significant differences in the affinity of these drugs binding to proteins: oxaliplatin>cisplatin>carboplatin. Further investigation was on protein-oxaliplatin binding in a group of colorectal cancer patients treated with oxaliplatin. Inter-patient variation in protein-drug binding was evident from the concentrations and nanoESI-MS spectra of protein-oxaliplatin complexes in patient blood samples. Multivariate analysis of the potential predictors using the Cox model showed a statistically significant correlation between Hb-oxaliplatin complex concentration and time-to-progress (p=0.02). These results suggest the Hb-oxaliplatin complexes in RBC as a potential biomarker for optimizing personalized treatment. |
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Mass Spectrometry of DNA and Protein Damages
8:10 AM-11:55 AM, Wednesday, August 22, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |