Project description
Research training network to study nicotinamide adenine dinucleotide signalling and biosynthesis in cancer
Deregulation of nicotinamide adenine dinucleotide (NAD) signalling and the upregulation of its biosynthetic enzymes nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase are linked to cancerogenesis, increasing cell proliferation, motility, de-differentiation and immune escape. NAD signalling and biosynthesis deregulation were shown to be present in solid and haematological malignancies. Funded by the Marie Skłodowska-Curie Actions programme, the INTEGRATA project will provide interdisciplinary training in drug discovery to young researchers, focusing specifically on NAD production and signalling as targets for developing new cancer therapeutics. Mainly, INTEGRATA aims to study the therapeutic potential of NAMPT as an anticancer drug target.
Objective
Deregulated nicotinamide adenine dinucleotide (NAD) biosynthesis and signaling underlies many aspects of carcinogenesis. NAD biosynthetic enzymes, such as nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), are commonly upregulated in cancer cells, where they fuel increased metabolic demands and downstream enzymes involved in DNA repair and in the promotion of cell growth, cell motility, de-differentiation and immune escape. In addition, NAD-producing enzymes, such as NAMPT, moonlight in the extracellular space, exerting strongly pro-oncogenic, autocrine and paracrine effects. Many of these roles of NAD-producing and NAD-utilizing enzymes appear to be shared between solid and haematological cancers. Thus, agents targeting NAD production or signaling are expected to have broad applicability. INTEGRATA will: 1. develop new NAD biosynthesis and NAD/nucleotide signaling inhibitors; 2. assess pharmacology and toxicity of the new therapeutics in preclinical models; 3. achieve the proof-of-concept of activity of the newly generated agents in relevant in vivo cancer models. INTEGRATA will train 14 PhD students in an overarching, interdisciplinary training programme that will include training-by-research, joint courses of technical, scientific, and transferrable skills, active participation to public scientific events, and an intense intersectoral networking exchange plan. The INTEGRATA Consortium encompasses academic institutions, research centres, and SMEs/biotech pharma, all with proven experience in higher education and training, and geared with state-of-the-art scientific and technical expertise and infrastructures.
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16126 Genova
Italy