Études des modifications épigénétiques dans les leucémies pédiatriques et identification de nouveaux traitements

 

Elodie Da Costa

Centre de recherche du CHU Sainte-Justine

 

Domaine : cancer

Programme Formation de doctorat

Concours 2019-2020

Partenaire:

Fondation des Étoiles

Paediatric leukemia represents the leading cause of mortality by disease for children although, nowadays, the survival rate is 82%. However, these treatments are extremely toxic, given that 2/3 of children suffer from severe side effects such as neurocognitive disorders, metabolic disease and apparition of secondary tumours. Side effects are caused by anticancer drugs' unspecific mechanisms that target cancer cells as much as healthy cells. The aim of my research project is to develop more efficient and less toxic therapeutic strategies by testing the anticancer efficacy of approved drugs, used to treat several disorders (cardiac diseases, diabetes, infections…), against cancer cells. This strategy is called drug repurposing. My objective is to repurpose approved drugs to improve the treatment of paediatric leukemia with a better tolerability than classical chemotherapeutic regimens. Particularly, I am interested in drugs that reprogram cancer cells and re-establish normal gene function. This therapeutic approach is known as epigenetic therapy of cancer. The results of my research will be used as groundwork to create new clinical trials that will be conducted in our research Center.

Our results have demonstrated that proscillaridin, a drug used to treat heart failure, exhibits potent anticancer and epigenetic efficiencies against cancer cells with safe doses for healthy cells. Proscillaridin induces oncogenic gene inhibition, responsible for the multiplication of cancer cells, and tumour suppressor gene activation, responsible for inducing a non-pathological profile to cancer cells. More advanced studies are currently validating our new therapeutic strategy before transitioning to a clinical trial.