This article proposes the first 'cells to society' research framework for appendiceal tumours, systematically integrating six core priority areas—pathology, molecular characteristics, tumour microenvironment, and health disparities—providing a comprehensive strategic direction for mechanistic research and precision therapy in this rare cancer.
Literature Overview
The article, 'Defining a ‘cells to society’ research framework for appendiceal tumours,' published in Nature Reviews. Cancer, reviews and summarizes current research progress and challenges in appendiceal tumours regarding pathological classification, molecular mechanisms, tumour microenvironment, metastasis mechanisms, and health disparities. It presents six core research priority areas established through expert consensus. The article systematically constructs the first comprehensive 'cells to society' research framework, aiming to advance basic and translational research on appendiceal tumours and improve clinical diagnosis and treatment. This framework encompasses not only mechanistic exploration at the molecular and cellular levels but also emphasizes coordinated advancement in macro-level societal aspects such as standardized histopathology, biorepository development, and health equity. The paragraph is coherent and logical, ending with a Chinese period.Background Knowledge
Appendiceal tumours are rare gastrointestinal malignancies with an annual incidence of approximately 0.12 cases per million people. However, their incidence in the United States has increased by 232% in recent years. Due to the lack of specific symptoms and screening tools, most patients are diagnosed only after the tumour has spread to the peritoneum, resulting in highly variable outcomes and 5-year survival rates ranging from 10% to 63%. These tumours exhibit strong histopathological heterogeneity, including subtypes such as mucinous, non-mucinous adenocarcinoma, goblet cell adenocarcinoma, and signet ring cell carcinoma. However, existing classification systems suffer from inconsistent terminology and ambiguous grading criteria, leading to low diagnostic concordance. At the molecular level, appendiceal tumours differ significantly from colorectal cancer, commonly exhibiting mutations in KRAS, GNAS, and TP53, yet comprehensive multi-omics studies remain lacking. The tumour microenvironment is rich in lymphoid tissue and unique microbial communities, which may influence immune responses and metastatic pathways. Furthermore, the absence of standardized animal models and high-quality biorepositories severely limits mechanistic research and drug development. This study addresses these challenges by proposing an integrated multi-level research strategy to bridge the gap between basic discoveries and clinical translation, advancing systematic and precision research in rare cancers.
Research Methods and Experiments
This study was conducted by the Appendiceal Cancer and Pseudomyxoma Peritonei Research Foundation (ACPMP), which convened a multidisciplinary team of experts using the nominal group technique to reach consensus on six core research priority areas for appendiceal tumours. The research systematically reviewed current literature on pathological classification, molecular features, tumour microenvironment, metastasis mechanisms, biorepository development, and health disparities in appendiceal tumours, identifying key challenges and knowledge gaps. By integrating clinical, pathological, genomic, and immunological microenvironment data, the study proposes a comprehensive 'cells to society' research framework that spans the entire research pipeline from molecular mechanisms to societal health equity. The framework emphasizes the application of cutting-edge technologies such as digital pathology, single-cell and spatial omics, and patient-derived organoids and PDX models, and advocates for the establishment of multicenter, diverse biorepositories and molecular atlases.Key Conclusions and Perspectives
Research Significance and Prospects
This study provides a systematic research blueprint for the rare tumour field, breaking away from traditional one-dimensional research models and advocating cross-scale, interdisciplinary integration. By establishing standardized pathological workflows and multi-omics atlases, molecular subtyping and precision diagnosis of appendiceal tumours may become feasible, improving patient stratification and outcome prediction.
Future research can leverage this framework to advance biorepository development, create disease-specific models, and explore immune microenvironment regulatory mechanisms. Additionally, incorporating health disparities into research will help achieve more equitable healthcare access and treatment outcomes.
Conclusion
This article systematically proposes the first 'cells to society' research framework for appendiceal tumours, integrating six priority areas: pathological standardization, molecular characterization, tumour microenvironment research, metastasis mechanisms, biorepository development, and health disparity analysis. This framework not only addresses major current challenges in the diagnosis, classification, and model systems of appendiceal tumour research but also provides a strategic direction for future mechanistic exploration and precision therapy. By promoting multi-omics integration and interdisciplinary collaboration, it may uncover unique carcinogenic mechanisms in appendiceal tumours and enable the development of specific targeted strategies. At the same time, the emphasis on digital pathology and computational models can enhance diagnostic accessibility and consistency, especially in resource-limited settings. Ultimately, the framework advocates incorporating health equity into research, ensuring that findings benefit all patient populations. This comprehensive approach sets a new paradigm for rare tumour research and is expected to accelerate the translation of basic discoveries into clinical applications, improving patient outcomes and quality of life.
