Final Report Summary - E.E.T.-PIPELINE (European Embryonal Tumor Pipeline)
Second to accidents, cancer is still the leading cause of death for children in Europe. Approximately 30 % of childhood malignancies are embryonal tumours (ET), often demonstrating resistance to conventional treatment approaches and being associated with lower survival rates compared to other childhood cancers. Thus, novel diagnostic and therapeutic options are urgently needed in particular for this group of tumours to improve survival rates and quality of life of paediatric cancer patients in Europe.
The project therefore focussed their combined research efforts on ET. ET are dysontogenetic tumours whose pathological features resemble those of the developing organ or tissue of origin and include the entities neuroblastoma (NB), nephroblastoma/Wilms' tumour (WT), medulloblastoma (MB), retinoblastoma (RB), the Ewing sarcoma family of tumours (ESFT) and rhabdoid tumours (RT). Their early manifestation in infants and young children suggests that only a limited number of genetic changes lead to the transformed phenotype, making ET an ideal model for the post-genomic investigation of cancer-related expression changes.
Due to the high genetic complexity of solid tumours in adults, it is difficult to identify suitable drug targets. The genetic low complexity of ET tumours provides a more suitable system to identify targets, which may also be important for adult tumours, and therefore, have a more general impact. Treatment of embryonal tumours (ET) is a challenge for the paediatric oncologist. Innovative translational research is required to exploit available genomic data and implement state-of-the- art technologies to overcome the deficits of current diagnostic and treatment strategies.
A consortium of leading European institutions and SMEs with extensive clinical and technological expertise was set up to establish a unique pipeline for the comprehensive development and validation of novel diagnostic tools in addition to efficient preclinical drug development for ET. The E.E.T.-PIPELINE provided a comprehensive, multi-team approach for improving ET diagnostics and treatment by the integration, assessment and validation of information generated by basic research utilising high-throughput technologies.
In this integrated post-genomic research effort, they established dual pipelines concentrating on (1) state-of-the-art diagnostics and (2) innovative drug development and preclinical testing to channel these efforts. Efficient use and distribution of resources as well as optimised data analysis and fast gain of molecular knowledge was ensured by linking both pipelines to a central bioinformatics platform. Meta-analysis integrating newly obtained and existing data for the ET entities derived from different genomic and proteomic platforms derived further gain of knowledge from the data. The driving force of the project was a set of 10 additional work packages (WPs), each specifically addressing the integration of a key technological platform in the ET diagnostics and drug development pipelines and making all platforms available for use by all consortium partners.
Due to the relatively low patient numbers in paediatric oncology, treatment of patients in nationwide or mostly Europe-wide clinical trials is mandatory and has been well established for decades. The realisation of the E.E.T.-PIPELINE efficiently bridged state-of-the-art post-genomic research at the bench and the bedside at the European level. The continuing existence of the E.E.T.-PIPELINE consortium of researchers, and its involvement in the ENCCA network of excellence for paediatric oncology provides a strengthened link towards rapid translation of 'omics'-derived results into clinical application.
As cancer is a major threat to the health of the approximately 160 million children < 15 years of age in Europe, and ET account for approximately 30 % of paediatric cancers, there is a considerable market for diagnostic and therapeutic tools developed in the E.E.T.-PIPELINE. Combined research on all ET tumour entities is a novel way of increasing the potential market for drugs and diagnostic tools for ET. Drugs effective against the group of ET entities may also be applicable to other morphologically related adult cancers, including melanomas and lung cancers, further increasing the potential markets.
The project therefore focussed their combined research efforts on ET. ET are dysontogenetic tumours whose pathological features resemble those of the developing organ or tissue of origin and include the entities neuroblastoma (NB), nephroblastoma/Wilms' tumour (WT), medulloblastoma (MB), retinoblastoma (RB), the Ewing sarcoma family of tumours (ESFT) and rhabdoid tumours (RT). Their early manifestation in infants and young children suggests that only a limited number of genetic changes lead to the transformed phenotype, making ET an ideal model for the post-genomic investigation of cancer-related expression changes.
Due to the high genetic complexity of solid tumours in adults, it is difficult to identify suitable drug targets. The genetic low complexity of ET tumours provides a more suitable system to identify targets, which may also be important for adult tumours, and therefore, have a more general impact. Treatment of embryonal tumours (ET) is a challenge for the paediatric oncologist. Innovative translational research is required to exploit available genomic data and implement state-of-the- art technologies to overcome the deficits of current diagnostic and treatment strategies.
A consortium of leading European institutions and SMEs with extensive clinical and technological expertise was set up to establish a unique pipeline for the comprehensive development and validation of novel diagnostic tools in addition to efficient preclinical drug development for ET. The E.E.T.-PIPELINE provided a comprehensive, multi-team approach for improving ET diagnostics and treatment by the integration, assessment and validation of information generated by basic research utilising high-throughput technologies.
In this integrated post-genomic research effort, they established dual pipelines concentrating on (1) state-of-the-art diagnostics and (2) innovative drug development and preclinical testing to channel these efforts. Efficient use and distribution of resources as well as optimised data analysis and fast gain of molecular knowledge was ensured by linking both pipelines to a central bioinformatics platform. Meta-analysis integrating newly obtained and existing data for the ET entities derived from different genomic and proteomic platforms derived further gain of knowledge from the data. The driving force of the project was a set of 10 additional work packages (WPs), each specifically addressing the integration of a key technological platform in the ET diagnostics and drug development pipelines and making all platforms available for use by all consortium partners.
Due to the relatively low patient numbers in paediatric oncology, treatment of patients in nationwide or mostly Europe-wide clinical trials is mandatory and has been well established for decades. The realisation of the E.E.T.-PIPELINE efficiently bridged state-of-the-art post-genomic research at the bench and the bedside at the European level. The continuing existence of the E.E.T.-PIPELINE consortium of researchers, and its involvement in the ENCCA network of excellence for paediatric oncology provides a strengthened link towards rapid translation of 'omics'-derived results into clinical application.
As cancer is a major threat to the health of the approximately 160 million children < 15 years of age in Europe, and ET account for approximately 30 % of paediatric cancers, there is a considerable market for diagnostic and therapeutic tools developed in the E.E.T.-PIPELINE. Combined research on all ET tumour entities is a novel way of increasing the potential market for drugs and diagnostic tools for ET. Drugs effective against the group of ET entities may also be applicable to other morphologically related adult cancers, including melanomas and lung cancers, further increasing the potential markets.
