Targeting Cannabinoid Receptors in HER2 positive tumours

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Overexpression of the receptor tyrosine kinase HER2 (ERBB2) leads to an aggressive form of breast cancer. While HER2-targeted therapies have improved the prognosis for HER2+ breast cancer, more research is required to understand biological mechanisms driving tumour progression. HER2 induces the expression of cannabinoid receptor 2 (CB2), which leads to a worse prognosis particularly when CB2 is expressed in lymph node metastases. We will test combination therapies using novel proprietary compounds in conjunction with HER2+ therapies. Next, we will examine the applicability of targeting either receptor with targeted degradation. Finally, using bioinformatics, multiplexed immunofluorescence imaging of patient samples and in vitro 3D models, we will study changes in the immune microenvironment of CB2+ HER2+ compared to CB2- HER2+ tumours.