PIPgen · PI3K/PTEN-related monogenic disease to understand cancer

PI3K/PTEN-related monogenic disease to understand cancer

PI3K signalling constitutes a key molecular node controlling growth, migration, survival, and metabolism. PIPgen aims to understand the PI3K/PTEN pathway in two pathological scenarios: cancer and PI3K-related monogenic rare diseases. There are more than 7000 rare diseases, affecting approximately 30 million EU citizens. Eighty percent of rare diseases have genetic origin and are often chronic or life-threatening. Hence, while each of these diseases is rare, collectively they affect a large population and represent a significant health burden. Interestingly, several of these genetic mutations are also implicated in cancer, a fundamental biological problem of Epidemic Proportions (>14 million new cases/year worldwide). Genetic alterations in the phosphoinositide 3-kinase (PI3K)/PTEN pathway are a common event in both monogenic rare diseases and in cancer. PIPgen stems from the emerging links between monogenic rare diseases and cancer, and how an integrated research on both fields can cross-fertilise to improve their understanding and treatment. Monogenic diseases offer ‘clean’ molecular, cellular and organismal information about the affected genes, whereas cancer is a compendium of genetic and epigenetic perturbations illustrative of complex diseases. Given the strong link between PI3K deregulation and cancer, multiple small molecules targeting the PI3K pathway have been generated. Currently several PI3K inhibitors have been approved for clinical use in cancer and several high-quality drugs are making their way to the clinic. Recent observations from this translational and clinical studies are becoming extremely informative for the assessment and the treatment of cancer but also opens new opportunities for exploitation for PI3K related monogenic rare diseases, a critical unmet medical need. The scientific objectives of PIPgen were addressed through five complementary work packages (WPs), each focusing on specific aspects of PI3K/PTEN-related pathologies.WP5-6 focused on monogenic rare diseases associated with PI3K/PTEN alterations, WP7-8 study cancer and WP9 acted as a transversal package dedicated to developing innovative tools and methodologies to support and to be applied in WP5-8. The multidisciplinary PIPgen network was composed of 11 leading European experts on the PI3K/PTEN field: academic partners, translational and clinical units and two industrial partners. PIPgen trained 15 ESRs in PI3K/PTEN-related diseases, equipping them with advanced scientific knowledge, leadership, project-management, communication, and ethical skills, a strong scientific identity, and cross-sector exposure to foster innovation, entrepreneurship, and long-term collaborations in the European biomedical landscape.

Data: CORDIS, © European Union