Background. Sunitinib is a tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma. The main difficulty related to the treatment is the development of drug resistance followed by rapid progression of the disease.
We analyzed tumor tissue of sunitinib treated patients in order to find miRNAs associated with therapeutic response Methods A total of 79 patients with metastatic renal cell carcinoma were included in our study miRNA profiling in tumor tissue samples was performed by TaqMan Low Density Arrays and a group of selected miRNAs (miR-155, miR-374-5p, miR-324-3p, miR-484, miR-302c, and miR-888) was further validated by qRT-PCR Normalized data were subjected to ROC and Kaplan-Meier analysis Results We reported decreased tissue levels of miR-155 and miR-484 as significantly associated with increased time to progression (miR-155: median TTP 5 8 versus 12 8 months, miR-484: median TTP 5 8 versus 8 9 months) Conclusion miR-155 and miR-484 are potentially connected with sunitinib resistance and failure of the therapy miR-155 is a known oncogene with direct influence on neovascularization Biological role of miR-484 has to be clarified Stratification of patients based on miRNA analysis would allow more personalized approach in therapy of metastatic renal cell carcinoma
BioMed research international 2015 May 03 [Epub]
Jana Merhautova, Renata Hezova, Alexandr Poprach, Alena Kovarikova, Lenka Radova, Marek Svoboda, Rostislav Vyzula, Regina Demlova, Ondrej Slaby
Department of Pharmacology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic , Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic ; Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic , Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic , Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic , Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic , Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic ; Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic , Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic , Department of Pharmacology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic , Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic ; Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic