Molecular Profiling of Druggable Targets in Clear Cell Renal Cell Carcinoma Through Targeted RNA Sequencing
| العنوان: | Molecular Profiling of Druggable Targets in Clear Cell Renal Cell Carcinoma Through Targeted RNA Sequencing |
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| المؤلفون: | Anne van Ewijk, Tessa J. J. de Bitter, Peter F.A. Mulders, Carolien Zeelen, William P.J. Leenders, Corina N. A. M. van den Heuvel, Egbert Oosterwijk, Martijn A. Huynen |
| المصدر: | Frontiers in Oncology, Vol 9 (2019) Frontiers in Oncology, 9 Frontiers in Oncology |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, renal cell carcinoma, medicine.medical_treatment, precision therapy, RNA-sequencing, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Renal cell carcinoma, prognostics, Gene expression, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], medicine, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], diagnostics, cancer, Survival rate, Original Research, Kidney, Sunitinib, business.industry, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Nephrectomy, Clear cell renal cell carcinoma, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, single molecule molecular inversion probes, business, Tyrosine kinase, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], medicine.drug |
| الوصف: | Clear cell renal cell carcinoma (ccRCC) comprises more than 80% of all renal cancers and when metastasized leads to a 5-year survival rate of only 10%. The high rate of therapy failure and resistance development calls for reliable methods that provide information on the actionable biological pathways and predict optimal treatment protocols for individual patients. We here applied targeted RNA sequencing (t/RNA-NGS) using single molecule Molecular Inversion Probes on tumor nephrectomy samples of five ccRCC patients, comparing tumor with healthy kidney tissues. Transcriptome profiling focused on expression of genes with involvement in ccRCC biology that can be targeted with clinically available drugs. Results confirm high expression of vascular endothelial growth factor-A (VEGF-A) in tumor tissue relative to healthy-appearing kidney, in line with the angiogenic nature of ccRCC. PDGFRα and KIT, targets of the multi-kinase inhibitor sunitinib which is one of the current choices of first-line drug in metastasized ccRCC patients, were expressed at relatively low levels in tumor tissues, whereas significantly increased in normal kidney. Of all measured druggable tyrosine kinases, MET, AXL, or EGFR were expressed at higher levels in tumors than in normal kidney tissues, although intertumor differences were observed. Using cancer cell lines we show that t/RNA-NGS gene expression profiles can be used to predict in vitro sensitivity to targeted drugs. In conclusion, t/RNA-NGS analysis may provide insights into the (druggable) molecular make-up of individual renal cancers, and may guide personalized therapy of renal cell cancers. |
| وصف الملف: | application/pdf |
| تدمد: | 2234-943X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca902e7730f1a5bc62c66d37ece71be2 https://hdl.handle.net/https://repository.ubn.ru.nl/handle/2066/202089 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ca902e7730f1a5bc62c66d37ece71be2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2234943X |
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