Advances in Biomarkers and Novel Therapeutics in Renal Cell Carcinoma: Evidence from Recent Clinical Trials.

Renal cell carcinoma (RCC) is the most common renal malignancy in adults. Owing to its high incidence, asymptomatic presentation, late diagnosis, and resistance to conventional therapies, it is associated with significant morbidity and mortality. However, current clinical trials focus more on identifying suitable molecular biomarkers and evaluating new treatments, such as targeted agents and immunotherapy. This review highlights novel biomarkers and recent clinical trials for the therapeutic management of patients with RCC. A comprehensive literature review was conducted using databases such as Web of Science, MEDLINE, Scopus, PubMed, and ClinicalTrials.gov (https://clinicaltrials.gov/) on novel biomarkers and various clinical trials for RCC. Recent clinical trials have shown a significant increase in biomarker discovery, including DNA methylation, microRNAs, long non-coding RNAs, and protein-based markers, which influence diagnosis, prognosis, and treatment. The treatment of RCC has progressed from cytokine-based immunotherapy to targeted therapies, such as mTOR and VEGF inhibitors, immune checkpoint inhibitors, and combination regimens, which have greatly improved patient outcomes. Emerging approaches, including novel immunological targets, adoptive cell therapies, vaccines, and oncolytic virotherapy, hold promise for overcoming resistance and boosting efficacy, and are currently being investigated in clinical trials. Despite these developments, intratumoral heterogeneity, lack of prognostic biomarkers, disparities in clinical trials, and treatment resistance are major limitations. Ongoing research and clinical trials focused on biomarker-driven precision medicine and combination approaches are expected to improve RCC management significantly. Validation through large multicenter trials will be necessary to enable the use of biomarkers for precision medicine in routine practice.