Integrating chemical and biological approaches to target NAD production and signaling in cancer
INTEGRATA is an European Training Network (ETN) funded in the framework of the H2020 Marie Skłodowska- Curie ITN programme. The INTEGRATA network aims at the education of promising Early Stage Researchers (ESRs) who will learn the key steps of the modern discovery process of new drugs and therapeutic approaches (i.e. enzyme inhibition measurements, toxicities on cell cultures, preliminary pharmacological parameters, and in vivo PoC studies), focusing specifically on NAD production and on NAD/nucleotide signaling as targets for the development of new cancer therapeutics.
A strong reliance on a sustained biosynthesis of NAD has emerged as one of the hallmarks of cancer. Features that are commonly encountered in cancer cells and that are thought to underlie their need to support NAD production include aberrant metabolic processes, increased cell proliferation and cell migration, and, perhaps most importantly, the need to face constant NAD consumption by NAD-degrading enzymes involved in DNA repair (e.g. PARP, SIRT6), cell signalling (e.g. CD38, CD73), or prevention of apoptosis (e.g. SIRT1, SIRT6). Thus, interrupting NAD production, or specifically targeting enzymes from the NAD/nucleotide signaling apparatus, is considered a very appealing and novel approach in oncology and one of the most promising areas of investigation for the development of new drugs.
The project is based on a profound interaction between the academic and industrial sectors, encompassing academic institutions, research centres, and SMEs, all with proven experience in higher education and training and geared with state-of-the art scientific and technical expertise and infrastructures. By combining the beneficiaries’ expertise in cancer research, medicinal chemistry, biochemistry, drug design, mAb manufacture, purification and characterization, as well as clinical haematology and oncology, together with experience in project management, INTEGRATA will create a multidisciplinary environment, where fourteen ESRs will exploit the tremendous potential of NAD-producing enzymes and of NAD/nucleotide-signaling as targets for treating cancer.
INTEGRATA aims at leveraging the existing (academic and industrial) European expertise in translational cancer research, NAD biology, synthetic chemistry, computer-assisted drug design and therapeutic Ab production to train a new generation of ESRs in what has become a central aspect in cancer biology and cancer treatment, NAD biosynthesis and NAD-driven biological processes, exposing them to all of the key steps of process that leads to the establishment of a new agent or of a new treatment strategy, as well as to the strategic planning and entrepreneurial spirit that are applied in real-life industrial settings.
The ultimate goal of our training programme is the creation of a core group of experts with interdisciplinary skills in NAD biology, cancer metabolism and drug development, that will go well beyond current programmes and leading to a broader approach to cancer treatment that is expected to attain a deeper vision of the problem of cancer metabolism, and to propose valid, new therapeutic solutions. Concomitantly, the ESRs will acquire transferable skills which will lead them to become the new leaders of academic or industrial research.
Coordinator: Prof Alessio Nencioni, University of Genova, Department of Internal Medicine and Medical Specialities, Genova, ITALY