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Nano-technology enabled repositioning of Disulfira.. (NANODISCAN)
Nano-technology enabled repositioning of Disulfiram as an anti-cancer stem cell agent
(NANODISCAN)
Date du début: 5 juin 2014,
Date de fin: 4 juin 2016
PROJET
TERMINÉ
Most cancers remain ‘incurable’ and life-thretening. Cancer stem cells (CSCs) are the source of chemo/radioresistance and responsible for cancer recurrence which suggests the urgent requirement of CSC-targeting drugs. Drug development is a slow (15 years/drug) and costly (US$1.5bn/drug) procedure with only 5-25% of new oncology drugs in clinical development actually reaching the market mainly due to the toxicity of novel molecules. This dilemma has led to an increasing appreciation of the potential of repurposing of known drugs. We have demonstrated that Disulfiram (DS), an old anti-alcoholism drug, possesses excellent anti-CSC activity with low toxicity to normal cells. Whereas its cancer clinial indication is limited by its bio-instability (~4 min half-life in blood stream). Our pilot data demonstrated that the anticancer efficacy of DS is significantly improved when mild extending its half-life by liposome encapsulation. In this study, the Incoming Fellow, who has very strong technical knowhow in cancer research, molecular pharmacology, anticancer drug development and nano-encapsulation, will bring novel nano-biomaterials invented in China into Europe. Taking advantage of the state-of-the-art facilities, CSC models, pharmaceutical resarch and developmental expertise and scientific/technical support from the Incoming Host and the other European collaborators, we will develop a long-circulating nano-encapsulated DS. The anticancer activity of the nano-encapsulated DS will be examined in vitro and in vivo in breast and liver cancer cell lines as well as the relevant CSC models. This study will pave the path for clinical trial of DS in cancer indication. The significance of this project will be: 1. Expand and extend our FP7-IRSES (2011-16) platform to strenthen long-term collaboration between China and EU partners; 2. Develop a new cancer therapeutics for the benefic of healthcare in Europe; 3. Open a new drug developmental window to benefit European economy.
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