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Updated: May 30, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Immunotherapy and targeted therapy combinations in renal cancer
1Biologic Therapy Program, Beth Israel Deaconess Medical Center, Boston, MA, USA. dmcdermo@bidmc.harvard.edu
Abstract:
In recent years an improved understanding of renal cell carcinoma (RCC) tumor biology has translated into major advancements in the treatment of patients with metastatic RCC. These novel therapies include inhibitors of the vascular endothelial growth factor (VEGF) pathway, and inhibitors of the mammalian target of rapamycin (mTor) pathway. In contrast to the results seen with molecularly targeted therapies, the administration of high-dose bolus IL-2 (HD IL-2) can produce durable responses in a small percentage of patients. While the substantial toxicity and limited efficacy that is associated with HD IL-2 limits its application, novel immunotherapies may be able to produce durable benefit with less toxicity. Once the standard of care, the role of low-dose single-agent cytokines is now limited in patients with RCC. However, combinations of cytokines with targeted therapy may have merit. The advent of targeted therapy in RCC does not eliminate the potential utility of immunotherapy but rather requires a rational refinement of this approach through improvements in patient selection and combination therapy that may increase the cure rate for patients with this disease.
Insights
Recent advancements in metastatic renal cell carcinoma (RCC) treatment include targeted therapies like VEGF and mTOR inhibitors. Novel immunotherapies offer potential durable benefits with reduced toxicity compared to high-dose IL-2.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Metastatic renal cell carcinoma (RCC) treatment has evolved with improved understanding of tumor biology.
- Novel targeted therapies, including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors, have emerged.
- High-dose interleukin-2 (HD IL-2) offers durable responses in a subset of patients but has significant toxicity.
Purpose of the Study:
- To review the advancements in metastatic RCC treatment.
- To evaluate the role of novel immunotherapies and targeted therapies.
- To explore potential combinations of cytokines with targeted therapies for improved outcomes.
Main Methods:
- Literature review of recent studies on RCC treatment modalities.
- Analysis of efficacy and toxicity profiles of targeted therapies and immunotherapies.
- Discussion of the evolving role of cytokines in combination with novel agents.
Main Results:
- Targeted therapies (VEGF, mTOR inhibitors) represent a significant advancement in metastatic RCC treatment.
- Novel immunotherapies show promise for durable benefit with potentially less toxicity than HD IL-2.
- Low-dose cytokines have limited roles as single agents but may be beneficial in combination therapies.
Conclusions:
- Targeted therapy has transformed metastatic RCC treatment, but immunotherapy retains potential utility.
- Future directions involve rational refinement of immunotherapy through improved patient selection and combination strategies.
- Combining targeted therapies with immunotherapies may increase cure rates for patients with metastatic RCC.
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