The European Organisation for Research and Treatment of Cancer Pathobiology group and the young task force: A pan-tumor framework for translational oncology

Abstract

Progress in precision oncology depends on effective and well-coordinated collaboration between pre-clinical researchers and clinical investigators. In this setting, the European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology group (PBG) plays a key role in reinforcing the link between biological research and clinical investigation, facilitating the translation of biological and medical findings into clinical application, supporting the rigorous testing of molecular hypotheses in clinical trials, and providing multidisciplinary expertise for biomarker development and validation across different tumor types. A defining characteristic of the EORTC PBG is its pan-tumor perspective, which is consistent with the evolving molecular taxonomy of cancer and, through specialized expertise in molecular biology, pathology, biomarker development, and quality assurance, contributes to the activities of both the EORTC Translational Research Division and the Disease-Oriented Groups. This editorial outlines the scientific mission and achievements of the EORTC PBG, highlights the increasing contribution of Young and Early Career Investigators within the group, and emphasizes the importance of pathobiology-driven research in rare cancers, where unmet clinical needs remain considerable.

The advancement of precision oncology relies on well-integrated collaboration between pre-clinical researchers and clinical investigators, and the European Organisation for Research and Treatment of Cancer (EORTC) Pathobiology group (PBG) is central to strengthening this interface by linking biological and medical findings to clinical application, promoting the rigorous evaluation of molecular hypotheses in clinical trials, and providing the multidisciplinary expertise required for the development and validation of biomarkers across various tumor types. ¹ A distinctive feature of the EORTC PBG is its pan-tumor approach, which reflects the evolving molecular taxonomy of cancer and, through specialized skills in molecular biology, pathology, biomarker development and quality assurance, supports the Translational Research Division and the Disease-Oriented Groups of the EORTC. ²

This editorial provides an overview of the scientific mission and achievements of the EORTC PBG, highlights the growing contribution of the PBG Young & Early Career Investigators (Y-ECI), and underscores the importance of advancing pathobiology-driven research in rare cancers, where unmet clinical needs remain substantial.

The scientific mission of the EORTC PBG

The EORTC PBG plays a central role in identifying and validating clinically meaningful biomarkers while ensuring that translational endpoints are integrated into clinical trials with appropriate methodological rigor. ³

Over the years, the group has led the standardization of pre-analytical and analytical procedures, from tissue handling and fixation to nucleic acid extraction, assay development, and performance monitoring. This standardization is essential for multicentric clinical trials, where variability in sample processing can compromise biomarker reproducibility. ¹ Complementing this effort, the PBG has established rigorous frameworks for biomarker assessments, including inter-laboratory concordance, validation of commercial kits, and external quality control programs. ⁴ These activities remain crucial to ensure that biomarker results used for patient stratification or clinical decision-making are accurate and comparable across centers.

The PBG has also supported the creation of biobanks for human biological materials collected in various EORTC clinical trials, including the SPECTA platform, providing biological specimens and associated clinical data to enable rigorous translational research. ⁵

Finally, central pathology review remains a core mission of the PBG, contributing to diagnostic accuracy and improved prognostic assessment. Evidence from past EORTC initiatives—including studies in melanoma, mesothelioma, lymphoma, and soft-tissue sarcoma—demonstrates that centralized expert review substantially reduces inter-center variability, enhances the robustness of translational analyses, and enables the redefinition or molecular reinterpretation of tumor categories when required. ⁶

These contributions are exemplified by historical PBG achievements in biomarker development, such as the clinical validation of urokinase-type plasminogen activator and its inhibitor, plasminogen activator inhibitor type-1, in breast cancer, which evolved from retrospective observations to preclinical and clinical investigations led by the PBG. ¹

The emerging role of the PBG young task force

To sustain and amplify the mission of the PBG, the PBG Y-ECI initiative is established as a platform to engage early-career clinicians, translational and basic researchers in the EORTC group. Recently, the group has experienced rapid growth, accounting for 170 members in November 2025, representing 25 countries, with the largest contributions from Italy, Belgium, the United Kingdom, Germany, France, and Spain. This geographic diversity strengthens opportunities for multinational collaborations, fosters cross-country learning, and enriches the translational perspectives within the group.

The multidisciplinary profile of this network is one of its major strengths. Based on internal membership estimates, medical oncologists represent the largest subgroup (36%), followed by pathologists (17%), surgical oncologists (10%), radiation oncologists (9%), radiologists (8%), and nuclear medicine physicians (5%). Importantly, the network also includes a cohort of basic researchers (10%) who drive assay development and biomarker discovery. In addition, bioinformaticians and data scientists (5%) provide expertise, which is increasingly critical for multi-omics integration, digital pathology, and computational modelling.

Building on this multidisciplinary and international composition, the Y-ECI network could contribute to innovative clinical research formats such as window-of-opportunity trials, which are becoming increasingly valuable for biomarker discovery. In these studies, investigational agents are administered for a short period of time before definitive treatment, not to assess clinical efficacy, but to enable the collection of tumor and blood samples for translational analyses. As demonstrated in recent works in head and neck squamous cell carcinoma, this design is safe and particularly effective in identifying biomarkers that can predict treatment response, guide therapeutic selection, and minimize exposure to ineffective or toxic agents. ⁷ By bringing together clinicians, pathologists, basic researchers, and computational scientists within a coordinated framework, the Y-ECI initiative provides an ideal environment to support and advance such biomarker-driven research strategies in future precision oncology trials. ²

An area in which both the PBG and the PBG Y-ECI can play a decisive role is the field of rare cancers, which represent roughly one-quarter of all cancer diagnoses in Europe and are associated with poorer outcomes compared to more common malignancies.^3,5

As emphasized in the Rare Cancer Agenda 2030, these tumors require dedicated strategies and strong networking to avoid disparities and ensure access to specialized expertise. Precision oncology offers important opportunities—through molecular reclassification, biomarker-driven treatments, and tumor-agnostic approaches—yet progress remains challenged by small, heterogeneous cohorts and the need for highly standardized translational methods.^8,9

In this context, the strengths of the EORTC PBG are particularly relevant: consistent biospecimen handling and harmonized biomarker assessment are crucial for generating reliable data, while central pathology review, and increasingly digital pathology, help reduce diagnostic uncertainty and facilitate timely expert evaluation across centers. ⁹

In conclusion, the integration of high-quality pathobiology remains essential for advancing precision oncology and translating molecular insights into meaningful clinical benefit.

The PBG multidisciplinary structure, which integrates clinical, pre-clinical, and computational skills, provides the methodological rigor needed for reliable translational research. The window-of-opportunity trial designs offer a particularly powerful platform to accelerate biomarker discovery and validate molecular endpoints. By coordinating these diverse competencies within a pan-tumor framework, the EORTC PBG, along with the dynamism of Y-ECI, is uniquely positioned to deliver impactful advances in biomarker-guided cancer therapy, including in rare tumors where meaningful translational evidence is most urgently needed.