(2) Li Xiaoxi, Ren Weijun, Liu Ling, Liu Chuan, Chen Xiang. A Critical Reassessment of Tumor Metastasis Simulation in Murine Models: Insights Into Methodological Advances and Biological Relevance. Advanced Therapeutics. 2025;8(12):e00277. 

Abstract: Metastasis drives treatment failure and cancer mortality, yet preclinical studies still rely heavily on subcutaneous xenograft models that prioritize tumor growth over metastatic biology. This disconnection from clinical reality significantly contributes to the high failure rate of experimental therapies in trials. Here, current mechanistic insights is integrated into metastasis and critically assess transplantation models to inform rational model selection for metastasis research. Tumor transplantation models exhibit distinct dissemination patterns governed by implantation methodology rather than intrinsic tumor properties. Subcutaneous models, while technically accessible, predominantly assess primary tumor growth and fail to capture critical metastatic steps like intravasation, pre-metastatic niche formation, and organotropism. Orthotopic transplantation faithfully replicates native tissue microenvironments, enabling simultaneous assessment of tumor growth and metastatic potential. Intravascular models, while inducing rapid colonization, distort natural metastatic progression by skipping early dissemination stages. Metastatic site transplantation isolates microenvironmental impacts on tumor adaptation but fails to capture de novo metastatic initiation. Ultimately, three strategies is proposed for preventing metastasis: Eradicating circulating tumor cells, blocking colonization, and stifling outgrowth. This perspective catalyzes the strategic advancement of tumor metastasis models, thereby strengthening the reliability of preclinical findings and accelerating their clinical translation.

(1) Li Xiaoxi; Jiang Yong; Qian Hui ; Lymphoma dissemination is a pathological hallmark for malignant progression of B-cell lymphoma, Frontiers in Immunology, 2023, 14:1286411

Abstract: Extranodal lymphoma occurs in one-third of lymphoma patients and is a key indicator of the international prognostic index, associated with unfavorable outcomes. Due to the lack of ideal models, the causes and characteristics of extranodal lymphoma are greatly underexplored. Recently, we observed a high incidence of extranodal lymphoma in two types of mouse models with tropism for the brain and kidneys. These findings prompt us to rethink the pathological progression of lymphoma colonization in lymph nodes and non-lymphoid organs. Nodal lymphoma, primary extranodal lymphoma and secondary extranodal lymphoma should be biologically and clinically distinctive scenarios. Based on the observations in mouse models with extranodal lymphoma, we propose that lymphoma dissemination can be seen as lymphoma losing the ability to home to lymph nodes. The pathological process of nodal lymphoma should be referred to as lymphoma homing to distinguish it from benign hyperplasia. Lymphoma dissemination, defined as a pathological process that lymphoma can occur in almost any part of the body, is a key pathological hallmark for malignant progression of B-cell lymphoma. Reshaping cellular plasticity is a promising strategy to allow transformed cells to homing back to lymph nodes and re-sensitize tumor cells to treatment. From this perspective, we provide new insights into the pathological progression of lymphoma dissemination and its inspiration on therapeutic interventions. We believe that establishing extranodal lymphoma mouse models, identifying molecular mechanism governing lymphoma dissemination, and developing therapies to prevent lymphoma dissemination will become emerging topics for fighting relapsed and refractory lymphoma.