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Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy
Mohammadsaleh Jahangir1, Omid Yazdani2, Mohammad Saeed Kahrizi3
1Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy has become a game-changing therapeutic approach revolutionizing the treatment setting of human malignancies, such as renal cell carcinoma (RCC). Despite the remarkable clinical activity of anti-PD-1 or anti-PD-L1 monoclonal antibodies, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might ultimately favor cancer development in patients with clinical responses. In light of this, recent reports have signified that the addition of other therapeutic modalities to PD-1/PD-L1 blockade therapy might improve clinical responses in advanced RCC patients. Until, combination therapy with PD-1/PD-L1 blockade therapy plus cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor (ipilimumab) or various vascular endothelial growth factor receptors (VEGFRs) inhibitors axitinib, such as axitinib and cabozantinib, has been approved by the United States Food and Drug Administration (FDA) as first-line treatment for metastatic RCC. In the present review, we have focused on the therapeutic benefits of the PD-1/PD-L1 blockade therapy as a single agent or in combination with other conventional or innovative targeted therapies in RCC patients. We also offer a glimpse into the well-determined prognostic factor associated with the clinical response of RCC patients to PD-1/PD-L1 blockade therapy.
Insights
Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy shows promise for renal cell carcinoma (RCC). Combination therapies may improve responses and overcome resistance in advanced RCC patients.
Area of Science:
- Oncology
- Immunotherapy
- Renal Cell Carcinoma Research
Background:
- Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy has revolutionized cancer treatment, including for renal cell carcinoma (RCC).
- However, response rates to PD-1/PD-L1 inhibitors are limited, with many patients experiencing primary or acquired resistance.
- Combining PD-1/PD-L1 blockade with other therapies is being explored to enhance clinical outcomes in advanced RCC.
Purpose of the Study:
- To review the therapeutic benefits of PD-1/PD-L1 blockade therapy in RCC.
- To explore the efficacy of combining PD-1/PD-L1 blockade with other targeted therapies.
- To identify prognostic factors influencing clinical response to PD-1/PD-L1 blockade in RCC.
Main Methods:
- Review of current literature on PD-1/PD-L1 blockade therapy in renal cell carcinoma.
- Analysis of combination strategies involving PD-1/PD-L1 inhibitors with CTLA-4 inhibitors or VEGFR inhibitors.
- Examination of prognostic factors associated with treatment response.
Main Results:
- PD-1/PD-L1 blockade as a single agent has shown clinical activity in RCC.
- Combination therapies, including with ipilimumab (CTLA-4 inhibitor) and axitinib or cabozantinib (VEGFR inhibitors), are approved for first-line treatment of metastatic RCC.
- These combinations aim to improve response rates and overcome resistance observed with single-agent therapy.
Conclusions:
- Combination therapy holds significant potential to improve clinical responses in advanced RCC patients.
- Understanding prognostic factors is crucial for optimizing PD-1/PD-L1 blockade therapy selection and outcomes.
- Further research into novel combinations and predictive biomarkers is warranted for RCC treatment.
