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Chorafas Foundation Award 2014 - Catherine Clavel

DESIGN, IN VITRO AND IN VIVO EVALUATION OF TUMOR-SELECTIVE ORGANIC AND ORGANOMETALLIC ANTICANCER DRUGS, Thesis director: Prof. Paul Dyson

"For developing an original approach to tumour targeting that provides highly selective agents for cancer chemotherapy."

Conventional chemotherapy leads to severe side-effects as a lack of selectivity between cancer and noncancer cells, such as nephrotoxicity, blood disorders, fatigue, hair loss, nausea and vomiting. Application of mild hyperthermia can increase the cytotoxicity of anticancer drugs in tumour cells. We describe low molecular weight thermoactive organic and ruthenium-based drugs with fluorous chains that are selectively triggered by mild hyperthermia. Against a panel of human cancer cell lines and non-cancerous immortalized cells in vitro, the compounds show considerable chemo-thermal selectivity towards cancer cells (ca. 5 μM versus >500 μM for healthy cells) for compounds with the longest fluorous chain. Even in vivo, one of those molecules has shown a 90% tumor inhibition in the CAM model. Further in vivo studies in a mouse model for one of those new canticancer drugs has shown increased tumour reduction when used in combination with hyperthermia.



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