Periodic Reporting for period 1 - PIPgen (PI3K/PTEN-related monogenic disease to understand cancer)
Período documentado: 2021-07-01 hasta 2023-06-30
PIPgen is a multidisciplinary and cross-sectorial consortium that brings together 11 leading European basic and clinical scientists and industrial partners, experts in the PI3K/PTEN field. 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, focusing on the basic science but also on making a real therapeutic impact.
There are more than 7000 rare diseases, affecting approximately 30 million European Union 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 four 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.
With all this in mind, PIPgens aims to better understand the PI3K/PTEN pathway in both pathological scenarios to not only focus on the basic science but also to make a real therapeutical impact.
PIPgen scientific objectives will be tackled by 5 complementary work packages (WP) based on defined molecular processes, WP5-6 are focused on monogenic rare diseases with PI3K/PTEN alterations, WP7-8 study cancer and WP9 is a transversal package that will produce innovative tools to be applied in WP5-8. The scientific objectives of PIPgen are:
- WP5-Growth: study the molecular mechanisms that cause developmental overgrowth disorders (PIK3CA-related overgrowth disorders (PROS) and PTEN-hamartoma tumour syndrome (PHTS)).
- WP6-Immunodeficiency: study of the impact of PI3K mutations on immunity.
- WP7-Cancer-Intrinsic: understand the molecular and therapeutic relevance of PI3K pathway alterations in cancer cells.
- WP8-Cancer -Extrinsic: investigate the impact of PI3K pathway alterations in the non-cancerous cells inhabiting the tumour.
- WP9- Tools: identify candidate processes to be studied in the other WPs and to generate small molecule modulators to stimulate translational research and drug development.
The overarching training goal of PIPgen is to train a 15 Early Stage Researchers (ESR) in a wide range of scientific and complementary competences towards changing the European biomedical landscape in PI3K/PTEN-related diseases. To this end PIPgen has designed a training program that will provide ESRs with (1) scientific knowledge on PI3K/PTEN (2) confidence and leadership (3) uniqueness (4) an inherent capacity to communicate and interact with peers and with the non-scientific community (5) scientific integrity and adherence to the code of conduct.
There are more than 7000 rare diseases, affecting approximately 30 million European Union 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 four 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.
With all this in mind, PIPgens aims to better understand the PI3K/PTEN pathway in both pathological scenarios to not only focus on the basic science but also to make a real therapeutical impact.
PIPgen scientific objectives will be tackled by 5 complementary work packages (WP) based on defined molecular processes, WP5-6 are focused on monogenic rare diseases with PI3K/PTEN alterations, WP7-8 study cancer and WP9 is a transversal package that will produce innovative tools to be applied in WP5-8. The scientific objectives of PIPgen are:
- WP5-Growth: study the molecular mechanisms that cause developmental overgrowth disorders (PIK3CA-related overgrowth disorders (PROS) and PTEN-hamartoma tumour syndrome (PHTS)).
- WP6-Immunodeficiency: study of the impact of PI3K mutations on immunity.
- WP7-Cancer-Intrinsic: understand the molecular and therapeutic relevance of PI3K pathway alterations in cancer cells.
- WP8-Cancer -Extrinsic: investigate the impact of PI3K pathway alterations in the non-cancerous cells inhabiting the tumour.
- WP9- Tools: identify candidate processes to be studied in the other WPs and to generate small molecule modulators to stimulate translational research and drug development.
The overarching training goal of PIPgen is to train a 15 Early Stage Researchers (ESR) in a wide range of scientific and complementary competences towards changing the European biomedical landscape in PI3K/PTEN-related diseases. To this end PIPgen has designed a training program that will provide ESRs with (1) scientific knowledge on PI3K/PTEN (2) confidence and leadership (3) uniqueness (4) an inherent capacity to communicate and interact with peers and with the non-scientific community (5) scientific integrity and adherence to the code of conduct.
15 ESRs have been recruited for the programme and are currently working on their projects. All ESRs are actively involved in the network meetings, trainings and summer schools organized by PIPgen. As part of their training programs they also participate in weekly laboratory meetings, journal clubs, and courses on different topics organized by their hosting institutions or Universities. So far 4 secondments have been completed and one is currently on going.
During the period reported 3 Internal meetings have been organised: 1) Kick off meeting (KoM) that took place in Barcelona on September 2021; 2) 1st PIPgen Meeting in Bilbao on March 2022 and 3) 2nd PIPgen Meeting in Rotterdam. The KoM was the first meeting and only supervisors participated, it was a good opportunity for the partners to know each other and to ensure that all participants had a complete overview of the aims and structure of the project. During the 1st and 2nd internal meetings ESRs presented the progress of their projects and received feedback from the other network participants. During both meetings scientific as well as complementary workshops where organised where all ESRs have actively participated.
During this first reporting period ESRs have also participated in an online Summer School on Computational Biology organised by qGenomics and attended a business school organised by iOnctura at Genève.
During the period reported 3 Internal meetings have been organised: 1) Kick off meeting (KoM) that took place in Barcelona on September 2021; 2) 1st PIPgen Meeting in Bilbao on March 2022 and 3) 2nd PIPgen Meeting in Rotterdam. The KoM was the first meeting and only supervisors participated, it was a good opportunity for the partners to know each other and to ensure that all participants had a complete overview of the aims and structure of the project. During the 1st and 2nd internal meetings ESRs presented the progress of their projects and received feedback from the other network participants. During both meetings scientific as well as complementary workshops where organised where all ESRs have actively participated.
During this first reporting period ESRs have also participated in an online Summer School on Computational Biology organised by qGenomics and attended a business school organised by iOnctura at Genève.
The PIPgen network, composed of 11 leading European experts on the PI3K/PTEN field: academic partners, translational and clinical units and two industrial partners envisions to empower PI3K/PTEN research in Europe specially towards clinical translation. Pipgen partners have the common aim of making a real impact on the prevention, cure and therapy of PI3K/PTEN-related disease such as cancer and monogenic rare diseases.
This Training programme aims to empower ESRs to become the new generation of European Leaders on PI3K/PTEN and to prepare them for all types of science related career options. They programme offers scientific knowledge on cancer, PI3K related minor diseases, specific technological and complementary professional skills workshops on preclinical models, imaging, drug development, bioethics etc.. knowledge that will strength their professional skills and enhance their career prospects.
The PIPgen network will impact in different areas: ESRs, industry, academia, clinical units and patients, and we expect that 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.
This Training programme aims to empower ESRs to become the new generation of European Leaders on PI3K/PTEN and to prepare them for all types of science related career options. They programme offers scientific knowledge on cancer, PI3K related minor diseases, specific technological and complementary professional skills workshops on preclinical models, imaging, drug development, bioethics etc.. knowledge that will strength their professional skills and enhance their career prospects.
The PIPgen network will impact in different areas: ESRs, industry, academia, clinical units and patients, and we expect that 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.