Innovative ligands for nuclear receptors to eradicate cancer relapse

“根除”国际、多学科和跨部门抗癌药物研究和开发方案的目的是使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，如维甲酸受体(RAR)和维生素D受体(VDR)，在癌症的许多特征中起着关键作用，并构成现代癌症治疗的有效靶点。为了解决欧盟优先考虑的“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RARGamma拮抗剂和VDR激动剂的高度创新的双作用杂化化合物；3)为我们的化合物设计处方前策略；4)并开发一种新的、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细胞和转移潜能。同时，我们将评估PAN-RAR拮抗剂是否对化疗引起的中性粒细胞减少症有效。为了将RAR和VDR靶向化合物发展成可管理的药物，并为最终的商业化做好准备，我们将制定配方前战略。我们将产生一种新的、高度创新的基于组织浆细胞分析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，我们将培训博士生不仅在具有国际竞争力的水平上进行原创和独立的研究，而且赋予他们创造性、批判性和企业家精神，并坚持他们的目标。我们的联合体由8名学术受益者和1名产业界受益者以及12名相关合作伙伴提供培训和借调。

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.