Chromophobe renal cell carcinoma (ChRCC) is the second most common variant histology (non-clear cell) RCC. ChRCC is distinct from clear cell RCC (ccRCC) in terms of genetics, genomics, metabolism, cell of origin, and response to targeted and immune therapies. The pathogenesis of ChRCC remains unclear, but current data suggest two potential mechanisms: mTORC1 hyperactivation through PTEN pathway mutations and mitochondrial dysfunction leading to oxidative stress. There are no specific approved treatments for ChRCC, although some responses to tyrosine kinase and mTOR inhibitors have been observed. Response to immunotherapy is generally limited. Targetable pathways involving innate lymphoid cells/IL-15 and cysteine homeostasis/ferroptosis have recently been identified.
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