RESUMEN
Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. Here, we performed protein tyrosine kinase (PTK) profiling using PamChip® technology. The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib. Briefly, our results showed that 36 kinase substrates differs (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. In our assay, tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.
Asunto(s)
Carcinoma de Células Renales , Inhibidores de Proteínas Quinasas , Proteínas Tirosina Quinasas , Anilidas , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Humanos , Indazoles , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Factores de Crecimiento Nervioso , Compuestos de Fenilurea , Fosfatidilinositol 3-Quinasas , Fosfatidilinositoles/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/metabolismo , Piridinas , Pirimidinas , Quinolinas , Sulfonamidas , Sunitinib/uso terapéutico , Familia-src QuinasasRESUMEN
Since the 1990s, minimal access surgery has been utilized in urology. In the past 15 years, robotic surgery has evolved and become a natural part of minimal access surgery. The dissemination has been fast and the opportunity of prospective trials has been missed. Nevertheless, robotic surgery has obvious benefits for the surgeon and patient. Even though the scientific evidence is not strong, robotic surgery is here to stay. However, there are lessons to learn from the implementation of the da Vinci system with regards to patient safety and prospective evaluation of the new technology. The future of surgery will include technologies derived from robotic surgery.