Advanced in vitro models for renal cell carcinoma therapy design

Renal cell carcinoma (RCC) and its principal subtype, clear cell RCC, are the most diagnosed kidney cancer. Despite substantial improvement over the last decades, current pharmacological intervention still fails to achieve long-term therapeutic success. RCC is characterized by a high intra-and inter-tumoral heterogeneity and is heavily influenced by the crosstalk of the cells composing the tumor microenvironment, such as cancer -associated fibroblasts, endothelial cells and immune cells. Moreover, multiple physicochemical properties such as pH, interstitial pressure or oxygenation may also play an important role. These elements are often poorly recapitulated in in vitro models used for drug development. This inadequate recapitulation of the tumor is partially responsible for the current lack of an effective and curative treatment. Therefore, there are needs for more complex in vitro or ex vivo drug screening models. In this review, we discuss the current state-of-the-art of RCC models and suggest strategies for their further development.

Automated summary

Renal cell carcinoma (RCC), especially clear cell RCC, is the most common type of kidney cancer. The lack of long-term therapeutic success in current pharmacological intervention is due to the high heterogeneity of RCC and the complexity of its tumor microenvironment. In vitro models used for drug development often fail to recapitulate important elements of the tumor, leading to a lack of effective treatment. Therefore, more complex in vitro or ex vivo drug screening models are needed for RCC research.