Renal cell carcinoma (RCC), particularly the clear cell subtype, is a solid tumor characterized by a high degree of immune cell infiltration, progressive immune dysfunction, and favorable response to immune checkpoint inhibitors (ICIs). Dual checkpoint inhibition or single-agent ICIs with anti-angiogenic therapies have become the standard of care in the treatment of advanced and metastatic RCCs. Locally advanced and oligometastatic RCCs are distinct clinical categories that are characterized by local invasion and initially limited metastatic spread, respectively, with different therapeutic responses and prognoses compared to either localized or advanced diseases. Herein, we summarize the biology, treatment, and molecular profiling of RCCs, providing an update on the clinical trials pertaining to cancer patients with locally advanced and oligometastatic RCC. We also discuss molecular features that could contribute to a better understanding of the tumor biology driving locally advanced and oligometastatic RCC.
International journal of molecular sciences. 2026 Feb 26*** epublish ***
Temitope M Ogunmola, Zeng Jin, Jeremy Kleberg, Tanzia Islam Tithi, Seyedehalaleh Anvar, Chandra K Maharjan, Jonathan Alexander Chatzkel, Sara Moscovita Falzarano, Ryan Kolb, Myung-Chul Kim, Weizhou Zhang
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA., UF Health Cancer Center, University of Florida, Gainesville, FL 32610, USA., Laboratory of Clinical Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.