Innovative ligands for nuclear receptors to eradicate cancer relapse

“根除”国际、多学科和跨部门癌症药物研究和开发计划的目标是使10名年轻科学家成为癌症研究和药物开发方面的专家，同时开发新的治疗方法，防止癌症干细胞驱动的复发和转移。视黄酸受体（RAR）和维生素D受体（VDR）等核受体在癌症的许多特征中起着关键作用，是现代癌症治疗的有效靶点。为了解决欧盟优先“癌症使命”，我们将1)测试RAR和VDR靶向化合物的抗癌活性；2)设计和合成一种高度创新的双作用杂化化合物，同时作为RARgamma拮抗剂和VDR拮抗剂；3)为我们的化合物制定配方前策略；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细胞和转移潜力。同时，我们将评估泛rar拮抗剂对化疗诱导的中性粒细胞减少症是否有效。为了将RAR和VDR靶向化合物开发成可给药药物，为最终的商业化做好准备，我们将制定制剂前战略。我们将产生一种新颖的，高度创新的基于组织等离子细胞术的无标签图像分析方法。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，我们将培养博士候选人（dc）不仅要在国际竞争水平上进行原创和独立的研究，而且要赋予他们创造性，批判性和创业精神，以及坚持不懈地遵循自己的目标。我们的联盟包括8个学术和1个工业受益人，以及12个提供培训和借调的合作伙伴。

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.