Plateforme provasculaire et immunothérapeutique ciblée anti-cancer par microbulles et ultrasons

 

Francois Yu

Centre hospitalier de l'Université de Montréal [CHUM]

 

Domaine : cancer

Programme Chercheurs-boursiers - Junior 1

Concours 2018-2019

Despite the recent successful development of numerous and diversified cancer therapies, these treatments still trigger important systemic toxicities and are curative in subsets of patients. Therefore, it is deemed essential to design novel strategies and approaches to override such limitations and improve the efficacy of our arsenal against cancer. Spatial targeting of anti-tumor therapies can maximize the specificity of such therapies while reducing their systemic side effects and consequently enhance the overall efficacy of treatments against cancer. Microbubbles (MB) are intravascular contrast agents traditionally used as blood tracers for ultrasound (US) imaging. Interestingly, MB oscillate in an US field and can therefore interact with surrounding cells. In addition to the documented ability of MB to increase vascular and cellular permeability, I recently showed that MB and US can increase perfusion in skeletal muscle microvasculature by activating purinergic and nitric oxide mediated vasodilation.

My innovative results establish the feasibility of locally augmenting the entry of peripheral mediators within a specific body site. In this research program, I am proposing to develop two highly innovative ultrasound based image guided targeted therapies against cancer by exploiting these recently identified molecular pathways to enhance the efficacy of radiotherapy and immunotherapy against cancer. The rational design and evaluation of these strategies is described in this proposal, which culminates with in vivo efficacy studies in xenografted tumor mouse models. At term, the novel targeted therapies have tangible potential for clinical translation to patients since all the individual components of the proposed therapy are already present in the clinical setting. The multidisciplinary research teams and infrastructures at the Centre de recherche du centre hospitalier de l'Université de Montréal (CRCHUM) are uniquely positioned to allow the development and thorough evaluation of these innovative targeted therapies.