Identification and validation of predictive markers of toxicity

We will seek to identify genetic polymorphisms of importance for toxicity of chemotherapy as tools for personalized chemotherapy based on the individual´s genetic constitution. Materials (whole blood or tumour samples) will be collected in clinical trials on melanoma or lung cancer. DNA will be extracted using automated technology and single-nucleotide polymorphisms (SNPs) of importance for metabolism and transport of chemotherapeutic drugs will be analysed by pyrosequencing and chip-based technology. In addition, samples will be collected for determination of plasma concentrations of drug and metabolites by HPLC and LC-MS. The results will be compared to the severity of adverse drug reactions in the individuals as evaluated in the clinical trial protocols. The overall goal is to replace the standardized chemotherapy of today with personalized chemotherapy based on pre-treatment prediction of tolerance.

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