Effect of Target Therapy on the Content of Transcription and Growth Factors, Protein Kinase TOR, and Activity of Intracellular Proteases in Patients with Metastatic Renal Cell Carcinoma

• Published in: Bulletin of experimental biology and medicine Vol. 160; no. 6; pp. 798 - 801
• Main Authors: Spirina, L. V., Usynin, E. A., Kondakova, I. V., Yurmazov, Z. A., Slonimskaya, E. M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2016; Springer; Springer Nature B.V
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Calpain; Calpain - metabolism; Cancer; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - secondary; Care and treatment; Cell Biology; Everolimus - administration & dosage; Genetic transcription; Health aspects; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Internal Medicine; Kidney Neoplasms - drug therapy; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Laboratory Medicine; Metastasis; Middle Aged; Molecular Targeted Therapy; Nephrectomy; NF-kappa B - metabolism; Oncology; Pathology; Protein kinases; Pyrimidines - administration & dosage; Sulfonamides - administration & dosage; TOR Serine-Threonine Kinases - metabolism; Treatment Outcome; Tyrosine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism; transcription and growth factor; mTOR; renal cancer; intracellular proteases
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-016-3313-6

We analyzed the dynamics of the expression of transcription factors, VEGF and its receptor VEGFR2, serine-threonine protein kinase mTOR and activity of proteasome and calpain in patients with metastatic renal cancer during therapy with tyrosine kinase inhibitor Votrient and mTOR blocker Afinitor. The expression of hypoxic nuclear factor HIF-1α in the tumor tissue decreased during therapy with the target preparations. The decrease of VEGF and its receptor VEGFR2 was observed only in patients treated with mTOR inhibitor. The increase in calpain activity in the tumor tissue was observed in both groups. These findings extend our understanding of the mechanism of action of target anticancer preparations as allow considering the studied markers as predictors in choosing optimal therapy.