Abstract 2419: Predicting clinical response based on ex vivo drug response in renal cell carcinoma using kinase activity profiling

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.2419-2419
• Main Authors: Ruijtenbeek, Rob, Houkes-van Kerkhoff, Liesbeth, Hilhorst, Maria, Mulders, Peter, Oosterwijk-Wakka, Jeannette, Kiemeney, Lambertus, Oosterwijk, Egbert
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-2419

Introduction: Sunitinib, a potent multitargeted receptor tyrosine kinase inhibitor, is the first line treatment for metastatic renal cell carcinoma (mRCC). Because sunitinib responses and toxicity are highly variable, there is a need for biomarkers predicting sunitinib response or predicting the optimal sequence preference when using alternative tyrosine kinase inhibitors. The aim of this study was to investigate the correlation between ex vivo drug response and clinical response in renal cell carcinoma (RCC) and to explore alternative treatment options. This study has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 259939. Methods: Protein tyrosine kinase activity profiles were generated on PamChip® peptide microarrays of lysed tumor resection tissues (1-5mm3) from 22 mRCC patients. The ex vivo effect of kinase inhibitors (sunitinib, axitinib, sorafenib, pazopanib, erlotinib and crenolanib) was determined and analyzed with Bionavigator software. A two-group (sunitinib responders versus non-responders) comparison applied on the inhibition ratios identified the significantly different peptide phosphorylations. Peptides were clustered according to their correlation with clinical response. Results: As little as 5 μg protein input (0.05 mm3 tissue) was used per kinase activity profile. The ex vivo sunitinib effect positively correlated with clinical responses especially in the subgroup which received sunitinib as 1st line treatment (4 responders vs. 4 non-responders). 18 of the 105 peptides were significantly (p