Chromophobe renal cell carcinoma: addressing the translational gap toward precision oncology for advanced disease

Chromophobe renal cell carcinoma (chRCC) represents a distinct histological subtype of kidney cancer. While typically characterized by an indolent clinical course, it presents significant management challenges in advanced or late-stage disease. This review presents current evidence regarding chRCC histopathology, emerging biomarkers, and proposed grading systems. We comprehensively analyze the molecular landscape, highlighting TP53 and PTEN mutations alongside characteristic chromosomal losses, while evaluating the role of epigenetic modifications and the immune microenvironment. Crucially, the paper details the mechanisms through which mitochondrial dysfunction and metabolic reprogramming drive chRCC pathogenesis. By assessing contemporary clinical trials, this work underscores the necessity for novel therapeutic interventions and the collection of large-scale prospective data to address current gaps in treatment. A precision oncology framework for chRCC should prioritize reproducible diagnosis, cautious biomarker validation, and prospective rare-tumor trials to refine risk stratification and management.