AUTHOR=Wang Xiaoqian , Wei Luling , Liu Runchang , Wang Xuezhe , Luan Xinchi , Li Xiaoxuan , An Haoran , Zhao Ruizhe , Qiu Yue 

TITLE=Gastric metastasis of renal cell carcinoma: features, mechanisms, and insights from existing literature

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1656858

DOI=10.3389/fcell.2025.1656858

ISSN=2296-634X

ABSTRACT=Renal cell carcinoma (RCC), a malignancy characterized by an increasing global incidence, exhibits a tendency for metastatic dissemination. However, gastric metastases, often identified in multicenter case series with an incidence of 0.2%–0.8%, typically present years after nephrectomy (median interval ∼6.7 years) and are associated with a poor prognosis (5-year OS ∼21% in historical cohorts). Gastric metastases typically present years after nephrectomy as either isolated or polymetastatic lesions, often accompanied by severe upper gastrointestinal symptoms and presenting significant clinical challenges. Mechanistically, the progression of metastasis is driven by dysregulated signaling pathways, including PI3K/AKT, Ras/MAPK, and Wnt/β-catenin, which facilitate epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and angiogenesis. The gastric microenvironment further contributes to tumor adaptation through metabolic stress, immune evasion, and exosome-mediated intercellular communication. Clinically, oligometastatic disease may benefit from surgical resection in combination with immunotherapy, whereas polymetastatic cases necessitate systemic therapies such as tyrosine kinase inhibitors and immune checkpoint blockers, albeit with limited efficacy. Emerging multi-omics approaches and single-cell sequencing technologies hold promise for elucidating organ-specific tropism and refining personalized treatment strategies. This review highlights the critical need to integrate mechanistic insights with innovative therapeutic interventions to improve outcomes for patients with gastric metastasis of RCC.