EAU 2014 - Predicting targeted therapy tumor resistance in renal cell carcinoma patient-derived xenografts implanted into chicken embryos - Session Highlights

STOCKHOLM, SWEDEN (UroToday.com) - A third of patients with metastatic RCC will have resistance to targeted agents, and even more patients will develop resistance over time. Concerns regarding toxicity, high cost, resistance, and genetic testing have limited the ability to offer personalized therapy. The ability to predict patient response prior to the initiation of treatment could improve patient outcomes. Dr. C. R. Mazzola and colleagues developed a patient-derived xenograft model to determine the sensitivity of each RCC patient’s tumor cells to a defined targeted therapy prior to the start of systemic treatment. The investigators developed a patient−derived xenograft model using chicken embryos that allows evaluation of the interplay between angiogenesis and tumor growth and direct drug application to tumors to evaluate their sensitivities. Seven patient-derived primary RCC cell lines were implanted into the chorioallantoic membrane (CAM) of chicken embryos to assess the effect of sunitinib on tumor take ratios.

eauThree cell lines known to be sensitive to sunitinib (XP206, XP158, XP185) and four known to be resistant to sunitinib (XP127, XP121, XP258, PF22) were utilized. A secondary cell line that is sensitive to sunitinib (786-0) was also implanted as a control. In the control group, tumor take rates were 82% in vehicle treated tumors compared to 46% in sunitinib treated tumors. Using the 7 patient-derived RCC cell lines implanted into the CAM, tumor take rates varied amongst cell lines. Overall, decreased tumor take rates were observed in sunitinib-sensitive cell lines treated with sunitinib when compared to their vehicle-treated control counterparts. Extensive angiogenesis was observed among tumor xenografts.

In conclusion, the CAM model evaluated in this pilot study demonstrated the ability to predict sensitivity to sunitinib therapy using patient derived RCC cell lines. The authors have developed a useful model for drug sensitivity evaluation that may enable clinicians to potentially individualize targeted treatments to each patient with metastatic RCC prior to the start of systemic therapy. Future studies will focus on additional drugs commonly used to treat RCC.

Presented by C. R. Mazzola at the 29th Annual European Association of Urology (EAU) Congress - April 11 - 15, 2014 - Stockholmsmässan - Stockholm, Sweden.

Western University, Dept. of Surgery, London, Ontario, Canada

Written by Jeffrey J. Tomaszewski, MD, medical writer for UroToday.com