Combination of Anti-Angiogenics and Immunotherapies in Renal Cell Carcinoma Show Their Limits: Targeting Fibrosis to Break through the Glass Ceiling?

Abstract

This review explores treating metastatic clear cell renal cell carcinoma (ccRCC) through current therapeutic modalities—anti-angiogenic therapies and immunotherapies. While these approaches represent the forefront, their limitations and variable patient responses highlight the need to comprehend underlying resistance mechanisms. We specifically investigate the role of fibrosis, prevalent in chronic kidney disease, influencing tumour growth and treatment resistance. Our focus extends to unravelling the intricate interplay between fibrosis, immunotherapy resistance, and the tumour microenvironment for effective therapy development. The analysis centres on connective tissue growth factor (CTGF), revealing its multifaceted role in ccRCC—promoting fibrosis, angiogenesis, and cancer progression. We discuss the potential of targeting CTGF to address the problem of fibrosis in ccRCC. Emphasising the crucial relationship between fibrosis and the immune system in ccRCC, we propose that targeting CTGF holds promise for overcoming obstacles to cancer treatment. However, we recognise that an in-depth understanding of the mechanisms and potential limitations is imperative and, therefore, advocate for further research. This is an essential prerequisite for the successful integration of CTGF-targeted therapies into the clinical landscape.