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、跨部门癌症药物研发计划的目标是让 10 名年轻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)，在癌症的许多特征中发挥着关键作用，并构成现代癌症治疗的有效靶点。为了解决欧盟优先事项“癌症使命”，我们将 1)测试RAR和VDR靶向化合物的抗癌活性； 2）设计并合成一种高度创新的双作用混合化合物，同时充当RARγ拮抗剂和VDR激动剂； 3）为我们的化合物设计预配制策略； 4）并开发一种新颖的、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细胞性和转移潜力。与此同时，我们将评估泛 RAR 拮抗剂是否能有效对抗化疗引起的中性粒细胞减少症。为了将 RAR 和 VDR 靶向化合物开发为可给药药物，为最终商业化做好准备，我们将制定预配制策略。我们将产生一种基于组织胞浆细胞计数的新颖且高度创新的无标记图像分析方法。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，我们将培训博士生（DC），不仅能够在国际竞争水平上进行原创和独立研究，而且能够赋予他们创造性、批判性和创业思维，并坚持不懈地追求自己的目标。我们的联盟由 8 名学术受益者和 1 名工业受益者以及 12 家提供培训和借调的相关合作伙伴组成。