INITIATOR

The ability of cancer to spread from the primary tumor to other organs by the process called metastasis is the leading cause of patient mortality worldwide. To date, the precise molecular mechanisms defining metastasis in cancer patients remain largely elusive. Inflammation plays a significant role in cancer progression and metastasis by creating an environment that supports tumor growth, invasion, and spread. To reduce the socio-economic burden, there is an urgent need to identify new molecular diagnostic and prognostic indicators of tumor aggressiveness to indicate the metastatic potential and to improve the accuracy of conventional clinical and histopathological assessments. These markers should define new molecular targets for drug design, particularly the use of inhibitors to treat aggressive metastatic cancers. Emerging studies highlight the crucial role of citrullination, post-translational modification of arginine to citrulline amino acid residues, in transcriptional plasticity and inflammatory regulation in tumor cells, which have been shown to represent hallmarks of aggressiveness in cancers. In this context, targeting citrullination at distinct stages of cancer progression (e.g., initiation, metastasis, acquisition of drug resistance) shows great promise for developing alternative adjunct therapies. These treatments, in combination with existing therapies, could improve treatment effectiveness and offer alternative options. The primary aim of the present consortium, which will form the core of a future doctoral network (DN), is to deepen the knowledge and understanding of citrullination changes that occur at primary and metastatic sites. The study of citrullination in tumor cells and the impact of cellular components of the microenvironment, combined with the design and testing of new pharmacological compounds, will serve as a platform for developing an interdisciplinary training program focused on tumor aggressiveness, epigenetics, structural biology, and the development of novel metabolism modulators. The overall goal of the proposed INITIATOR project is to assemble a consortium of internationally renowned experts in metastatic cancers, citrullination, inflammation, and the development of novel anti-tumor drugs to constitute a doctoral network proposal to the MSCA-DN-2025 call (MSCA-DN-2026, if not successful in 2025 call). The overall project will combine research-based training in the fields of citrullination, inflammation, and metastatic cancers. Our DN is committed to achieving scientific excellence along with incorporating the development of essential transferable skills, such as intellectual property management, communication, and entrepreneurship. Here, we have assembled a core consortium of relevant experts of international repute. The support from the MRSEI grant will enable us to enlarge and consolidate this core consortium by integrating the most appropriate new partners from both the public and private sectors, covering a large geographical area. The synergy of the partners' expertise will enhance the career prospects of up to 12 recruited doctoral candidates, providing them with better opportunities in the sectors they aspire to join.