Background/Aim: Sunitinib is a tyrosine kinase inhibitor routinely used as first-line therapy in metastatic renal cell carcinoma (mRCC). Emerging evidence suggests that microRNAs (miRNAs) could be suitable biomarkers with predictive potential in mRCC. The aim of this study was to identify miRNA-based predictive biomarkers of therapy response to avoid unnecessary therapy to non-responding patients. Patients and Methods: High-throughput miRNA microarray profiling was performed on a cohort of 47 patients treated with sunitinib. Validation of candidate miRNAs was carried out on an independent cohort of 132 mRCC patients using qRT-PCR. Results: Out of 158 miRNAs (65 down-regulated, 93 up-regulated), six miRNAs were chosen for independent validation and miR-376b-3p was confirmed to be differentially expressed in tumors of patients with primary resistance versus long-term response (p<0.0002). Conclusion: A predictive miRNA associated with progression-free survival in metastatic renal cell carcinoma patients treated with sunitinib was identified. Renal cell carcinoma (RCC) accounts for more than 3% of adult solid tumors and is fatal for around 40% of patients (1). The metastatic form of this disease (mRCC) is routinely treated with tyrosine kinase inhibitors (TKIs) of the VEGF pathway to prevent formation of new blood vessels that support tumors with nutrients. Sunitinib is routinely used as a first-line therapy, followed by other therapeutic options and TKI variants in the second-and third-line treatment after first line failure, which is inevitable in most patients (2, 3). However, duration of response is variable, ranging from a few months to more than two years since a proportion of the patients have primary resistance to treatment, some develop it faster than others (4). The financial burden of therapy together with many unpleasant side-effects affecting the quality of life of patients are the main drivers behind the attempts to identify predictive biomarkers reliably differentiating patients who would benefit from the first-line sunitinib from those who should be immediately redirected to other therapeutic options. MicroRNAs (miRNAs) are a class of short non-coding RNAs, 18-25 nucleotides long, post-transcriptionally regulating gene expression of more than half of protein-coding human genes. Complementary binding to the 3'untranslated region of their target mRNAs (5), miRNAs are pivotal regulators of many vital cellular processes and their deregulation leads to over-or 353 This article is freely accessible online.

Following further independent validation, detection of these miRNAs may prevent unnecessary and costly approaches to therapy in non-responding patients with mRCC.

Renal cell carcinoma (RCC) accounts for 2%-3% of all malignant tumours. The first-choice treatment in metastatic RCC (mRCC) patients is tyrosine kinase inhibitors (TKIs). Although TKIs may prolong survival of the treated patients who are not primary resistant, almost all of them will eventually develop secondary resistance to the treatment after a progression-free period. To predict treatment response, thus, we need efficient biomarkers for rational indication of TKIs in mRCC. MicroRNAs (miRNAs) not only play important roles in the pathogenesis of many cancers, including RCC but also have been shown to serve as promising diagnostic, prognostic and predictive biomarkers in various cancers. However, the potential of miRNAs to predict response to therapy with TKIs in mRCC has not yet gained sufficient attention. Because personalisation of the TKIs indication in mRCC presents an important unmet medical need, we summarise research on this topic and give an overall insight on the current knowledge in this field.