MicroRNAs (miRNAs) predict response to treatment with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC). The miRNAs define patients refractory to TKI therapy who have a poor prognosis. TKIs are antiangiogenic drugs used frequently to treat renal cell carcinoma.1
“There is a group of patients who are refractory to this therapy,” explained Cristina Rodríguez-Antona, the Hereditary Endocrine Cancer Group at the Centro Nacional de Investigaciones Oncológicas, Madrid, Spain, and senior author of the study, implying the tumor continues to grow despite treatment with these agent.
Identifying biomarkers improves understanding of prognosis, risk of recurrence, or sensitivity to various medications, as well as improve use of personalized therapies. Dozens of biomarkers that predict patients’ response to cancer medications are known, but no biomarkers had been discovered for metastatic renal cell carcinoma or for antiangiogenic medications used to treat the disease.
Researchers performed deep sequencing of miRNAs, small stable nucleotides that regulate several biologic processes, in tissue samples from 74 patients with metastatic renal cell carcinoma. Of these patients, 16 (22%) showed disease progression and 58 (78%) showed complete or partial responses to treatment or stabile disease.
From this analysis, 65 miRNAs were expressed significantly differently in early progressive tumors than stable tumors. Six of these miRNAs were easily detectable biomarkers selected for independent validation. Five were associated with poor response to TKIs and appeared independent of prognosis.
Next, the authors created a predictive model in a group of 132 patients with metastatic renal cell carcinoma. They considered the 5 differentially expressed miRNAs along with other clinical characteristics, such as prognostic group, age, and gender. After several analyses, researchers revealed a model based on 2 miRNAs that showed higher accuracy than any other clinical feature in predicting how tumors would respond to TKIs.
1. García-Donas J, Beuselinck B, Inglada-Pérez L, et al. Deep sequencing reveals microRNAs predictive of antiangiogenic drug response. JCI Insight. 2016 Jul 7. doi:10.1172/jci.insight.86051. [Epub ahead of print]