Targeting Cannabinoid Receptors in HER2 positive tumours

受体酪氨酸激酶HER2 （ERBB2）的过度表达导致一种侵袭性乳腺癌。虽然HER2靶向治疗改善了HER2阳性乳腺癌的预后，但还需要更多的研究来了解驱动肿瘤进展的生物学机制。HER2诱导大麻素受体2 （cannabinoid receptor 2, CB2）的表达，尤其当CB2在淋巴结转移中表达时，导致预后较差。我们将测试使用新型专有化合物与HER2+疗法结合的联合疗法。接下来，我们将研究靶向任一受体与靶向降解的适用性。最后，利用生物信息学、患者样本的多路免疫荧光成像和体外3D模型，我们将研究CB2+ HER2+与CB2- HER2+肿瘤相比免疫微环境的变化。

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.