Periodic Reporting for period 2 - PIPgen (PI3K/PTEN-related monogenic disease to understand cancer)
Okres sprawozdawczy: 2023-07-01 do 2025-09-30
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.
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.
From the launch of PIPgen to its conclusion, all activities outlined in the Description of Action were successfully implemented. Minor adjustments were introduced to accommodate the needs of specific research and training activities; however, all deliverables were submitted, all milestones were achieved and all secondments were completed as planned.
The full strategic training program was delivered. All 15 ESRs were recruited and actively participated in the network meetings, trainings and summer schools organized by PIPgen. In addition, as part of their training they took part in weekly laboratory meetings, journal clubs, and courses on various topics offered by their hosting institutions or Universities. PIPgen provided ESRs with scientific training on cancer, PI3K-related rare diseases and workshops on preclinical models, imaging, drug development, bioethics and more. Furthermore, ESRs received specialized technological and complementary professional skills training, which strengthened their professional competences and enhanced their career prospects.
All internal meetings were organized as foreseen: 1) Kick off meeting: that took place in Barcelona on September 2021; 2) 1st PIPgen Meeting in Bilbao on March 2022, 3) 2nd PIPgen Meeting in Rotterdam; 4) 3rd PIPgen Meeting in Toulouse; 5) 4th PIPgen meeting that took place in Cambridge on September 2024; 6) Final PIPgen Meeting, organized in Barcelona in May 2025.
Scientific progress was achieved across the 5 scientific Work Packages. To date, results have been published in 10 peer-reviewed publications with many additional manuscripts currently in preparation, and have been presented at numerous conferences in both oral and poster formats.
The consortium fostered a collaborative environment that enhanced scientific outcomes, helped ESRs build lasting professional relationships, and emphasized the value of teamwork. Annual meetings, workshops, and secondments promoted knowledge sharing and interdisciplinary research, leading to numerous new collaborations that will extend beyond the project.
During the second reporting period the most relevant communication activity organized within PIPgen was the PIPgeneratingArt project. An Art and science initiative that brought together artists, researchers and patients resulting in artworks inspired by the research projects of PIPgen ESRs.
The full strategic training program was delivered. All 15 ESRs were recruited and actively participated in the network meetings, trainings and summer schools organized by PIPgen. In addition, as part of their training they took part in weekly laboratory meetings, journal clubs, and courses on various topics offered by their hosting institutions or Universities. PIPgen provided ESRs with scientific training on cancer, PI3K-related rare diseases and workshops on preclinical models, imaging, drug development, bioethics and more. Furthermore, ESRs received specialized technological and complementary professional skills training, which strengthened their professional competences and enhanced their career prospects.
All internal meetings were organized as foreseen: 1) Kick off meeting: that took place in Barcelona on September 2021; 2) 1st PIPgen Meeting in Bilbao on March 2022, 3) 2nd PIPgen Meeting in Rotterdam; 4) 3rd PIPgen Meeting in Toulouse; 5) 4th PIPgen meeting that took place in Cambridge on September 2024; 6) Final PIPgen Meeting, organized in Barcelona in May 2025.
Scientific progress was achieved across the 5 scientific Work Packages. To date, results have been published in 10 peer-reviewed publications with many additional manuscripts currently in preparation, and have been presented at numerous conferences in both oral and poster formats.
The consortium fostered a collaborative environment that enhanced scientific outcomes, helped ESRs build lasting professional relationships, and emphasized the value of teamwork. Annual meetings, workshops, and secondments promoted knowledge sharing and interdisciplinary research, leading to numerous new collaborations that will extend beyond the project.
During the second reporting period the most relevant communication activity organized within PIPgen was the PIPgeneratingArt project. An Art and science initiative that brought together artists, researchers and patients resulting in artworks inspired by the research projects of PIPgen ESRs.
Beyond its scientific contributions in strengthening PI3K/PTEN research in Europe and advancing clinical translation, the training programme has empowered ESRs to become the new generation of European leaders in PI3K/PTEN and has prepared them for a wide range of science-related career options.
The PIPgen network impacted different areas: ESRs, industry, academia, clinical units, and patients, and we expected that in the future, PIPgen will not only have an impact on the knowledge and treatment of PI3K-related diseases but also increase the international competitiveness of European research in PI3K/PTEN. Furthermore, the project has cultivated strong collaborations across academic, clinical, and industrial sectors, ensuring the translation of findings into real-world applications.
PIPgen made significant progress in understanding how distinct mutations in PIK3CA drive vascular malformations, altering the endothelial function. We uncovered new regulatory mechanisms and therapeutic vulnerabilities that will guide future precision medicine strategies for immune disorders and solid tumors. We have also gained insights into the genetic determinants beyond the classical PIK3CA in rare disease, while developing new software for pathogenic variants.
Additionally, we have developed a new PI3K inhibitor with potential therapeutic application in PI3K-driven diseases, along with AI-based algorithms that could be integrated into clinical diagnostic workflows to reduce the time of diagnosis for rare diseases. PI3Kd inhibitors have been tested beyond blood malignancies with promising results.
The PIPgen network impacted different areas: ESRs, industry, academia, clinical units, and patients, and we expected that in the future, PIPgen will not only have an impact on the knowledge and treatment of PI3K-related diseases but also increase the international competitiveness of European research in PI3K/PTEN. Furthermore, the project has cultivated strong collaborations across academic, clinical, and industrial sectors, ensuring the translation of findings into real-world applications.
PIPgen made significant progress in understanding how distinct mutations in PIK3CA drive vascular malformations, altering the endothelial function. We uncovered new regulatory mechanisms and therapeutic vulnerabilities that will guide future precision medicine strategies for immune disorders and solid tumors. We have also gained insights into the genetic determinants beyond the classical PIK3CA in rare disease, while developing new software for pathogenic variants.
Additionally, we have developed a new PI3K inhibitor with potential therapeutic application in PI3K-driven diseases, along with AI-based algorithms that could be integrated into clinical diagnostic workflows to reduce the time of diagnosis for rare diseases. PI3Kd inhibitors have been tested beyond blood malignancies with promising results.