PRESSURE · Preventing Therapy Resistance in Esophageal Cancer Using Advanced Models and Molecular Signatures

Preventing Therapy Resistance in Esophageal Cancer Using Advanced Models and Molecular Signatures

CONTEXT | Esophageal adenocarcinoma (EAC) is a rapidly increasing cancer in Europe that still lacks effective, tailored treatments and clear, uniform care pathways. There is an urgent need for better therapies, tools to match the right treatment to the right patient, and more consistent treatment strategies across countries. Yet, the specialised expertise, data and experimental models needed to achieve this are scattered across Europe, and there is insufficient tumor biological knowledge in this disease area. The PRESSURE project brings together leading academic hospitals, research institutes, companies, insurers and patient organisations from nine EU Member States to build a common European response to EAC. It recognises that lasting progress requires not only new scientific insights but also better-trained experts, strong links between sectors, and close attention to patients’ needs, policies and real-world healthcare constraints. OBJECTIVES | PRESSURE has two closely linked main goals: First, it aims to improve EAC treatment and policy in Europe by creating a shared research infrastructure: experimental models, large clinical datasets and advanced analysis tools that allow the consortium to uncover why some patients respond to treatment while others do not, and if novel therapies can be identified. This includes developing new drug combinations and repurposed medicines, identifying predictive biomarkers, and generating real world response data that can underpin more rational, uniform treatment strategies.[8] Second, PRESSURE trains a new generation of highly skilled researchers who can work across medicine, biology, data science, industry, policy and patient advocacy, and who are able to take up positions in all sectors that directly or indirectly shape EAC care. A structured doctoral programme provides project management, ethics, epidemiology, advanced imaging, bioinformatics, intellectual property and business development training, supplemented by international secondments and exchanges. EXISTING EXPERTISE AND PRELIMINARY WORK | PRESSURE builds on a strong foundation of existing models, biobanks, data resources and long standing collaborations. Consortium members already maintain a large “living biobank” of patient derived EAC models, in vitro and in vivo systems and ex vivo tissue slice cultures, all supported by appropriate facilities and ethical approvals. Several national registries, notably in Sweden and the Netherlands, already provide high quality population based data on thousands of EAC patients per year, and efforts are underway to interrogate merged Scandinavian and Dutch registries. Biobanking initiatives have collected blood, stool, biopsy and resection specimens from many hundreds of patients, with data on clinical variables and outcomes. The partners also bring established expertise in imaging, sequencing, biomarker development, epidemiology and early phase clinical trials, and have previously collaborated in EU projects and guideline setting networks, ensuring that PRESSURE starts from a mature, well connected scientific and clinical community rather than from scratch. PATHWAY TO IMPACT | Scientifically, PRESSURE will create a unique platform of models and data packages that participating teams – and, over time, the wider community – can use to address key unanswered questions in EAC biology and treatment. Models will use advanced imaging data to predict treatment response, with strong safeguards for robustness, traceability, and avoidance of bias. Standardised data formats, data dictionaries and GDPR compliant handling of clinical variables will ensure that findings are reliable, reusable and shareable. Economically and technologically, the project is designed to feed directly into new products and services: revised treatment regimens, validated response biomarkers, and more uniform treatment strategies informed by real world data. These advances are expected to improve treatment effectiveness, reduce healthcare costs and patient distress, and may lead to clinical trials and spin off companies, strengthening European innovation capacity and competitiveness. Societally, a dedicated work package focuses on communication, dissemination and exploitation. PRESSURE actively engages scientists, clinicians, industry, policy makers, patient organisations and the general public through tailored communication activities, and high impact publications.

Data: CORDIS, © European Union