Translational In Vitro Models in Head and Neck Cancer: From Cellular Mechanisms to Clinical Correlates

Head and neck cancers present marked genetic heterogeneity, complex tissue architecture, and highly variable clinical behaviour. Histopathological features, such as patterns of invasion, stromal interactions, inflammatory responses, and cellular differentiation, reflect underlying molecular programs that ultimately determine prognosis and therapeutic response. Yet the mechanistic links between clinical applications, tissue-level observations and the cellular processes governing tumor adaptation remain only partially understood.This gap highlights the urgent need for preclinical models that more faithfully reproduce the histopathological and molecular complexity of patient tumors. Traditional two-dimensional cultures only partially capture the architecture, cell-cell interactions, and stress responses observed in vivo, while animal models, although informative, raise ethical considerations and often fail to reflect the full spectrum of human tumor diversity.This Research Topic welcomes contributions that address one or more of the following scientific goals:1) Advancing mechanistic understanding of how genetic alterations, signaling networks, metabolic rewiring, and stress-response pathways drive tumor heterogeneity, invasion, and therapeutic resistance, including links to clinical outcomes, prognostic markers, and histopathological features.2) Developing, refining, or validating in vitro models that recapitulate the structural, molecular, or functional properties of head and neck tumors, improving mechanistic insight and supporting precision medicine while adhering to 3Rs principles.3) Performing comparative analyses across in vitro systems, in vivo models, and human tissues to evaluate model fidelity, identify conserved mechanisms, and clarify where models succeed or fall short in representing clinical disease.4) Advancing translational approaches that connect molecular features, cellular phenotypes, and histopathological patterns to patient outcomes, including biomarker discovery, multi-omics integration, quantitative pathology, and imaging-based diagnostics to enhance risk stratification, early detection, or treatment selection.5) Introducing interdisciplinary innovations at the interface of anatomy, cell biology, bioengineering, toxicology, and clinical oncology to establish new concepts, tools, or analytical frameworks for studying head and neck tumor biology.6) Leveraging advanced experimental models to assess drug responses, elucidate mechanisms of therapeutic failure, test rational combination therapies, or identify patient-specific vulnerabilities, ultimately supporting individualized and more effective treatment strategies.By bringing together tumor biology with advanced modeling and integrating comparative, mechanistic, and translational studies that link cellular behavior, histopathological observations, and clinical trajectories, this Research Topic aims to accelerate discoveries that enhance prognostic precision, improve treatment personalization, and ultimately advance clinical care for patients with head and neck cancers.We welcome submissions including original research articles, mechanistic and translational studies, methodological papers, reviews, and perspectives that address the topics outlined above. Topic editors: Ludovica Gaiaschi, Serena Pellegatta Source: https://www.frontiersin.org/research-topics/84921/translational-in-vitro-models-in-head-and-neck-cancer-from-cellular-mechanisms-to-clinical-correlates