Angiogenesis Inhibitors and Immunomodulation in Renal Cell Cancers: The Past, Present, and Future

Simple Summary In their advanced stages, the mainstay of kidney cancer treatment is with medications such as targeted or immune therapies. Breakthroughs in scientific understanding of cancer drug development have led to substantial improvements in life expectancy. Although several combinations are available to choose from, it remains unclear which is best, and furthermore why cancers become resistant to treatment. This review article explores the scientific basis behind drug treatments in kidney cancers, with particular focus on blood vessel development and the immune system, and summarizes the available evidence supporting multi-drug treatments in this context. Angiogenesis inhibitors have been adopted into the standard armamentarium of therapies for advanced-stage renal cell carcinomas (RCC), but more recently, combination regimens with immune checkpoint inhibitors have demonstrated better outcomes. Despite this, the majority of affected patients still eventually experience progressive disease due to therapeutic resistance mechanisms, and there remains a need to develop novel therapeutic strategies. This article will review the synergistic mechanisms behind angiogenesis and immunomodulation in the tumor microenvironment and discuss the pre-clinical and clinical evidence for both clear-cell and non-clear-cell RCC, exploring opportunities for future growth in this exciting area of drug development.