Innovative ligands for nuclear receptors to eradicate cancer relapse.

The aim of the “eRaDicate” international, multidisciplinary, and intersectoral cancer drug research and development programme is to empower 10 young scientists to become specialists in cancer research and drug development, while developing new therapies against 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) design and synthesise a highly innovative dual action hybrid compound acting simultaneously as RARγ antagonist and VDR agonist; 3) devise pre-formulation strategies for our compounds; 4) and develop a novel, deep learning-based cancer analysis and diagnostics method. 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-induced neutropenia. For the development of the RAR and VDR targeting compounds into administrable medicines, ready for eventual commercialisation, we will develop pre-formulation strategies. We will generate a novel and highly innovative label-free image analysis 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 perform original and independent research on an internationally competitive level, but also endow them with creative, critical and entrepreneurial 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 and secondments.