Role of Biomarkers

The evolving treatment landscape in RCC continues to highlight a critical challenge: the lack of reliable biomarkers to guide therapy selection. Although clinical factors such as International mRCC Database Consortium risk help categorize patients, they don’t fully predict who will respond best to certain treatments like immunotherapy or VEGF inhibitors. The key to improving outcomes lies in identifying biomarkers that can tailor treatment to the individual patient’s tumor biology and likelihood of response.

Current promising biomarker research is primarily focused on RNA expression signatures, which classify tumors into distinct molecular subtypes. These signatures have been validated retrospectively in several large clinical trials and are beginning to be incorporated prospectively into new trials, such as one using RNA profiles to guide choices between immunotherapy combinations and targeted therapies. This represents a hopeful step toward personalizing treatment, moving beyond the one-size-fits-all approach. However, genomic alterations have proven less informative as biomarkers in RCC, limiting their clinical utility so far.

Beyond treatment sensitivity, biomarkers of residual disease and treatment response are gaining interest. Emerging tools such as KIM1, a protein biomarker, and ctDNA assays show promise for monitoring minimal residual disease and early treatment response, although these technologies remain largely experimental. As sequencing and detection methods advance rapidly, combining multiple biomarkers may one day enable precise, real-time treatment adjustments. Although the field is still in its early stages and no biomarkers are yet ready for routine clinical use, ongoing research provides optimism that a more effective, individualized therapy selection will become a reality in the near future.