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Updated: Sep 30, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
The roaring 2020s: a new decade of systemic therapy for renal cell carcinoma
Arnav Srivastava1, Sai K Doppalapudi1, Hiren V Patel1
1Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Purpose Of Review:
The genomic and immunologic profiling of renal cell carcinoma (RCC) has provided the impetus for advancements in systemic treatments using combination therapy - either with immune check point inhibitor (ICI) + ICI or with ICI + targeted therapy. This approach has been examined in several landmark trials, treating both clear cell (ccRCC) and nonclear cell (nccRCC) histologies. In this review, we highlight systemic therapy advancements made in this new decade, the 2020s.
Recent Findings:
Targeting the programmed death receptor 1/PD-L1 pathway has created more tolerable and effective immunotherapy regimens, expanding the applications of ICIs. These new applications, paired with trial data, include ICI monotherapy in nccRCC and adjuvant pembrolizumab in resected, high-risk RCC. In addition, ICI + ICI and ICI + TKI combination therapy have demonstrated oncologic efficacy in advanced ccRCC and sarcomatoid RCC. Similar progress has been noted regarding new targeted therapies. Along the hypoxia inducible factor pathway, belzutifan has received FDA approval in von Hippel-Lindau-associated RCC. In addition, in papillary RCC, agents such as cabozantinib target the MET proto-oncogene pathway and have demonstrated impressive oncologic outcomes.
Summary:
The 2020s utilize the molecular profiling of advanced RCC as a scaffold for recent trials in immunotherapy and targeted therapies. Going forward, emphasizing patient-reported outcomes and careful clinical trial construction remain critical to improve systemic therapy in RCC.
Insights
Recent advancements in renal cell carcinoma (RCC) systemic therapy include novel immune checkpoint inhibitor (ICI) combinations and targeted treatments. These therapies show promise for both clear cell (ccRCC) and nonclear cell (nccRCC) histologies.
Area of Science:
- Oncology
- Genitourinary Cancer
- Translational Medicine
Background:
- Genomic and immunologic profiling of renal cell carcinoma (RCC) has driven significant progress in systemic treatment strategies.
- Combination therapies, including immune checkpoint inhibitors (ICIs) alone or with targeted agents, are transforming RCC management.
- Recent landmark trials have evaluated these approaches in both clear cell (ccRCC) and nonclear cell (nccRCC) histologies.
Purpose of the Study:
- To review systemic therapy advancements in renal cell carcinoma (RCC) during the 2020s.
- To highlight the impact of immune checkpoint inhibitors (ICIs) and targeted therapies in various RCC subtypes.
- To discuss the evolving landscape of combination treatments for advanced and resected RCC.
Main Methods:
- Review of recent clinical trials and therapeutic developments in RCC.
- Analysis of data on immune checkpoint inhibitor (ICI) monotherapy and combination regimens.
- Evaluation of targeted therapies, including those acting on the hypoxia-inducible factor and MET pathways.
Main Results:
- Immune checkpoint inhibitor (ICI) + ICI and ICI + targeted therapy combinations show efficacy in advanced ccRCC and sarcomatoid RCC.
- ICI monotherapy is effective in nccRCC, and adjuvant pembrolizumab benefits resected, high-risk RCC.
- Targeted therapies like belzutifan (for VHL-associated RCC) and cabozantinib (for papillary RCC) demonstrate significant outcomes.
Conclusions:
- Molecular profiling of advanced RCC underpins current immunotherapy and targeted therapy trials.
- Future research must prioritize patient-reported outcomes and robust clinical trial design.
- Continued innovation in systemic therapy is crucial for improving outcomes in renal cell carcinoma.
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