Translational Research Bridging Basic and Clinical Insights in Renal Cell Carcinoma: A Collaborative Review and Future Directions.

Abstract

Despite significant progress in the diagnosis and treatment of renal cell carcinoma (RCC), approximately 20% of patients present with metastatic disease, and up to 30% of patients with localized tumors experience recurrence following nephrectomy. Although immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) have improved clinical outcomes, treatment resistance and refractoriness remain critical challenges. Genomic profiling has identified alterations in several kidney cancer-associated genes, including VHL and chromatin remodeling genes, refining the classification of RCCs and revealing novel therapeutic targets such as hypoxia-inducible factor (HIF)-2α and metabolic pathways. Immunologically, RCCs exhibit trends opposite to those observed in other types of cancer, such as melanoma and lung cancer, in that high tumor mutation burden and high CD8+ T cell infiltration in RCCs do not predict better responses to ICIs. Combination therapies integrating ICIs and VEGFR-TKIs have shown greater treatment efficacy, but overcoming immune resistance remains an urgent priority. Liquid biopsy technologies, including assays of circulating tumor DNA and extracellular vesicles, are emerging as minimally invasive tools for early detection, treatment monitoring, and recurrence prediction. Liquid biopsy approaches that Integrate genomic and transcriptomic profiling may provide comprehensive tumor characterization and suggest personalized treatment strategies. This review explores recent advances in basic and translational research, emphasizing genomic analyses, dissection of tumor-immune microenvironments, and liquid biopsy techniques that can reshape RCC diagnostics and therapeutics. Multidisciplinary collaboration supported by high-quality biospecimens and robust clinical datasets is essential to advance translational research and improve patient outcomes.