Recent Advances in Single-Cell RNA-Sequencing of Primary and Metastatic Clear Cell Renal Cell Carcinoma

SIMPLE SUMMARY: In recent years, several therapeutic advances have been made in clear cell renal cell carcinoma (ccRCC) resulting in novel treatment regimens of increased effectiveness. These advances are largely due to breakthroughs in technologies, particularly in transcriptomics, such as single-cell RNA sequencing (scRNA-seq). Using this technology, we have gained a deeper understanding of the biology of ccRCC and revealed various cell populations and their interactions in disease progression. While localized ccRCC patients have shown promising responses to treatment, however, patients with advanced or metastatic disease remain a therapeutic challenge. To address this gap, recent studies have utilized scRNA-seq to investigate both primary and metastatic ccRCC in search of promising therapeutic targets. This review aims to summarize the current state of knowledge in the field, highlight available treatment options and underscore the critical steps needed to improve survival rates, especially for metastatic ccRCC patients. ABSTRACT: Over the past two decades, significant progress has been made in the treatment of clear cell renal cell carcinoma (ccRCC), with a shift towards adopting new treatment approaches ranging from monotherapy to triple-combination therapy. This progress has been spearheaded by fundamental technological advancements that have allowed a deeper understanding of the various biological components of this cancer. In particular, the rapid commercialization of transcriptomics technologies, such as single-cell RNA-sequencing (scRNA-seq) methodologies, has played a crucial role in accelerating this understanding. Through precise measurements facilitated by these technologies, the research community has successfully identified and characterized diverse tumor, immune, and stromal cell populations, uncovering their interactions and pathways involved in disease progression. In localized ccRCC, patients have shown impressive response rates to treatment. However, despite the emerging findings and new knowledge provided in the field, there are still patients that do not respond to treatment, especially in advanced disease stages. One of the key challenges lies in the limited study of ccRCC metastases compared to localized cases. This knowledge gap may contribute to the relatively low survival rates and response rates observed in patients with metastatic ccRCC. To bridge this gap, we here delve into recent research utilizing scRNA-seq technologies in both primary and metastatic ccRCC. The goal of this review is to shed light on the current state of knowledge in the field, present existing treatment options, and emphasize the crucial steps needed to improve survival rates, particularly in cases of metastatic ccRCC.