Related Experiment Video
Updated: Dec 31, 2025
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy
Published on: April 29, 2014
Lessons from the A2A Adenosine Receptor Antagonist-Enabled Tumor Regression and Survival in Patients with
1New England Inflammation and Tissue Protection Institute, a Consortium at Northeastern University, Boston, Massachusetts. m.sitkovsky@northeastern.edu.
Abstract:
In this issue of Cancer Discovery, Fong and colleagues describe the encouraging observations of tumor regression, disease control, and survival of patients with otherwise refractory renal cell cancer with progressive disease after treatment with the conceptually novel oral antagonist of the A2A adenosine receptor (A2AR), ciforadenant. A2AR antagonists may represent the until now missing but critically important part of more effective immunotherapies of cancer, because they prevent the inhibition of tumor-reactive T and natural killer cells by blocking the immunosuppressive hypoxia-A2A-adenosinergic signaling, which represents an emerging immunosuppressive hallmark of tumors that are the most resistant to therapies.See related article by Fong et al., p. 40.
Insights
Novel oral A2A adenosine receptor (A2AR) antagonist ciforadenant shows promise in treating refractory renal cell cancer. This immunotherapy component may overcome tumor resistance by blocking immunosuppressive signaling.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) often becomes refractory to treatments.
- Tumor resistance is frequently associated with immunosuppressive signaling pathways.
- The A2A adenosine receptor (A2AR) pathway plays a role in tumor immunosuppression.
Purpose of the Study:
- To evaluate the efficacy of ciforadenant, an oral A2AR antagonist, in patients with refractory advanced renal cell cancer.
- To investigate the potential of A2AR antagonism as a component of cancer immunotherapy.
Main Methods:
- Clinical observation of patients with progressive, refractory renal cell cancer treated with ciforadenant.
- Assessment of tumor regression, disease control, and patient survival.
Main Results:
- Encouraging observations of tumor regression were noted.
- Disease control and improved survival were observed in patients with progressive disease.
- Ciforadenant demonstrated potential in overcoming treatment resistance.
Conclusions:
- A2AR antagonists like ciforadenant may be a critical component for enhancing cancer immunotherapy efficacy.
- Blocking the hypoxia-A2A-adenosinergic signaling can counteract tumor-induced immunosuppression.
- This approach holds promise for treating therapies-resistant tumors, including renal cell cancer.
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