Targeting Cannabinoid Receptors in HER2 positive tumours

靶向 HER2 阳性肿瘤中的大麻素受体

• 批准号: 2772066
• 金额: --
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2772066
• 关键词: Targeting; Cannabinoid; Receptors; HER2; positive

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.

受体酪氨酸激酶 HER2 (ERBB2) 的过度表达会导致乳腺癌的侵袭性。虽然 HER2 靶向疗法改善了 HER2+ 乳腺癌的预后，但仍需要更多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 (CB2) 的表达，这会导致更差的预后，特别是当 CB2 在淋巴结转移中表达时。我们将使用新型专利化合物与 HER2+ 疗法结合来测试联合疗法。接下来，我们将检查通过靶向降解来靶向任一受体的适用性。最后，我们将利用生物信息学、患者样本的多重免疫荧光成像和体外 3D 模型，研究 CB2+ HER2+ 与 CB2- HER2+ 肿瘤相比免疫微环境的变化。