Innovative ligands for nuclear receptors to eradicate cancer relapse

核受体的创新配体可根除癌症复发

• 批准号: EP/Y030818/1
• 负责人: Geoffrey Brown
• 金额: $ 33.22万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY030818%2F1
• 关键词: Innovative; ligands; nuclear; receptors; eradicate

The aim of the "eRaDicate" international, multidisciplinary, and intersectoral cancer drug research and development programme is toempower 10 young scientists to become specialists in cancer research and drug development, while developing new therapiesagainst cancer stem cell-driven relapse and metastasis. Nuclear receptors, such as retinoic acid receptor (RAR) and vitamin D receptor(VDR), play key roles in many hallmarks of cancer and constitute effective targets for modern cancer therapy.To address the EU priority "Mission Cancer", we will 1) test the anti-cancer activity of RAR and VDR targeting compounds; 2) designand synthesise a highly innovative dual action hybrid compound acting simultaneously as RARgamma antagonist and VDR agonist; 3)devise pre-formulation strategies for our compounds; 4) and develop a novel, deep learning-based cancer analysis and diagnosticsmethod.We will test how our RAR and VDR-targeting compounds affect stemness and metastatic potential in leukaemia, breast, prostate,colorectal, and ovarian cancer. In parallel, we will assess if the pan-RAR antagonist is effective against chemotherapy-inducedneutropenia. For the development of the RAR and VDR targeting compounds into administrable medicines, ready for eventualcommercialisation, we will develop pre-formulation strategies. We will generate a novel and highly innovative label-free imageanalysis method based on histoplasmonic cytometry. The project will have lasting scientific, economic, and societal impact.In order to be prepared for a wide spectrum of career opportunities, we will train the doctoral candidates (DCs) not only to performoriginal and independent research on an internationally competitive level, but also endow them with creative, critical andentrepreneurial mindset, coupled with persistence in following their objectives.Our consortium consists of 8 academic and 1 industrial beneficiary, as well as 12 associated partners to provide training andsecondments.

“eRaDicate”国际、多学科和跨部门癌症药物研发计划的目的是使10名青年科学家成为癌症研究和药物开发方面的专家，同时开发针对癌症干细胞驱动的复发和转移的新疗法。核受体如视黄酸受体（RAR）和维生素D受体（VDR）在许多癌症标志中起关键作用，是现代癌症治疗的有效靶点，为了应对欧盟优先的“使命癌症”，我们将1）测试RAR和VDR靶向化合物的抗癌活性; 2）设计和合成同时作为RAR γ拮抗剂和VDR激动剂的高度创新的双重作用混合化合物; 3）为我们的化合物设计预制剂策略; 4）开发一种新的基于深度学习的癌症分析和诊断方法。我们将测试我们的RAR和VDR靶向化合物如何影响白血病、乳腺癌、前列腺癌、结直肠癌和卵巢癌的干性和转移潜力。同时，我们将评估泛RAR拮抗剂是否对化疗诱导的中性粒细胞减少有效。为了将RAR和VDR靶向化合物开发成可服用的药物，为最终的商业化做好准备，我们将制定预制剂策略。我们将产生一个新的和高度创新的无标记的图像分析方法的基础上组织胞浆细胞计数。该项目将产生持久的科学，经济和社会影响。为了为广泛的职业机会做好准备，我们将培养博士生（DC）不仅要在国际竞争力水平上进行原创和独立的研究，还要赋予他们创造性，批判性和创业精神，我们的联合体由8名学术界和1名工业界受益者以及12名提供培训和借调的相关合作伙伴组成。