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Développement d’une bithérapie antitumorale basée sur une approche théranostique : applications aux cancers du cerveau et de la vessie

Abstract : Solid malignant tumors have molecular characteristics that clearly distinguish them from healthy tissue. The project is to develop a new therapeutic strategy based on these molecular characteristics. We set up a new therapeutic approach so as to customize treatment by connecting it directly to the diagnosis of the tumor (theranostic approach).Brain tumours and bladder tumours are two examples of particularly aggressive solid tumours. These two types of tumors are classified into several subgroups that have their own molecular profiles. The microRNAs (miR) are molecules naturally synthesized by cells. These molecules may have a role of oncogene or tumour suppressors whose expression is strongly deregulated in tumours. So the assessment of the expression levels of few microRNA allows the distinction of gliomas of high grade compared to low grade.To set up the new therapy we needed to modulate the expression of microRNAs deregulated in tumors. The proposed approach was to counter the expression of oncogenic microRNAs overexpressed using an antimicroARN (antimiR). This type of molecule is chemically similar to the naturally occurring RNA molecules in the cells. For a better efficiency of this new therapeutic strategy, we tried to optimize the transport of the antimiR to increase the therapeutic effect. To vectorize the therapeitic antimiR to the heart of the tumor, we envisioned to chemically combine the antimiR to a cell-penetrating antitumoral compound. Chalcones derivatives which are hydrophobic have this capability. A combination of the two molecules (antimicroARN and chalcone) was evaluated and the results appeared promising.
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Audrey Guttin. Développement d’une bithérapie antitumorale basée sur une approche théranostique : applications aux cancers du cerveau et de la vessie. Cancer. École pratique des hautes études - EPHE PARIS, 2016. Français. ⟨NNT : 2016EPHE3018⟩. ⟨tel-02101632⟩

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