INTRODUCTION: In recent years, molecular characterization of renal cell carcinoma has facilitated the identification of driver genes, specific molecular pathways, and characterization of the tumor microenvironment, which has led to a better understanding of the disease. This comprehension has revolutionized the treatment for patients with metastatic disease, but despite these advancements many patients will develop resistance leading to treatment failure. A primary cause of this resistance and subsequent treatment failure is tumor heterogeneity. We reviewed the literature on the mechanisms of tumor heterogeneity and its clinical implications. METHODS: A comprehensive literature search was performed using the MEDLINE/PubMed Index. RESULTS: Intertumor and intratumor heterogeneity is possibly a reason for treatment failure and development of resistance. Specifically, the genetic profile of a renal tumor differs spatially within a tumor as well as among patients. Genomic mutations can change temporally with resistant subclones becoming dominant over time. CONCLUSIONS: Accounting for intratumor and intertumor heterogeneity with better sampling of cancer tissue is needed. This will hopefully lead to improved identification of driver mutations and actionable targets. Only then, we can move past the one-size-fits-all approach toward personalized treatment based on each individual׳s molecular profile.
