Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

Ultrasound-stimulated microbubble (USMB) is a technique being used in pre-clinical and clinical settings, as a cancer therapy enhancer. Triple negative breast cancer (TNBC), an aggressive malignancy that lacks targeted therapies, is a prime candidate for USMB-mediated treatment. Currently, the effect of USMB on cancer cell death and adaptation remains poorly characterized. One effect is that cancer cell communication becomes altered in a subset of cells exposed to USMB to favour survival. In previous laboratory cell studies, we identified adenosine monophosphate activated protein kinase (AMPK), a nutrient sensor in human cells, to be a key player in this adaptation response. Blockage of AMPK in a petri-dish environment, resulted in greater cell death and reduced cancer cell survival. We aim to validate this effect of USMB on cancer signaling and survival in human breast cancer tumours grown in mice. We will use a modified TNBC cell line and an automated 3D USMB therapy system to establish TNBC tumours and perform USMB therapy. We hypothesize that tumours which do not produce AMPK will exhibit enhanced tumour cell death and lower tumour growth potential, after treatment with USMB. The objectives of the proposed study are to (1) investigate the role of AMPK in tumour adaptation responses in live mice and (2) validate the potential of the automated USMB therapy system for clinical application. This research may open avenues for targeted, combination therapies with USMB for an underserved patient population. Furthermore, the proposed study will be the first to validate the role of AMPK-mediated tumour adaptation to USMB therapy in mouse models, highlighting a new method with potential to overcome multiple therapy resistance in patients with few options.