Presentation Authors: Ravan Moret*, Xin Zhang, Grace Maresh, Daniel Canter, Marc Matrana, New Orleans, LA, Christudas Morais, Glenda Gobe, Queensland, Australia, Sunil Talwar, Maria Latsis, Stephen Bardot, Li Li, New Orleans, LA
Introduction: Renal cell carcinoma (RCC) incidence is increasing, and metastatic disease effects up to 25% of RCC patients. Additionally, RCC has varying prognoses and therapy responses, and metastatic RCC is incurable with a 5-year survival rate of < 10%. An avatar model can be used for screening the best treatment for individual cancer patients. In this model, various drugs can be applied to determine the best outcome, by mimicking patient response in a xenograft model. _x000D_
Our objective was to use an Avatar approach to compare the efficacy of various treatment combinations in alternating sequence in our unique patient-derived orthotopic xenograft (PDOX) model.
Methods: In our PDOX model, luciferase-tagged human RCC specimen cells (1Ã—105 KiCa-Pt58 cells or 3Ã—105 KiCa-Pt118 cells per mouse) were injected sub-capsularly into the left kidneys of NOD/SCID mice. Mice bearing kidney tumors were randomized into 1 control or 4 sequential treatment groups receiving sunitinib (40 mg/kg), pazopanib (40 mg/kg), or everolimus (5 mg/kg) three times per week via gavage (n=9-10). Tumor growth was monitored weekly by bioluminescent imaging (BLI). Drug responses were evaluated based on BLI data comparing treatment groups to control group and decisions made for mice that showed no inhibition of tumor growth to switch to the next sequence drug. All drugs were only changed once. Organs and tumors were collected upon necropsy for ex vivo BLI; tumor weights were recorded. Immunohistochemistry staining was done to confirm BLI findings.
Results: Selected drug dosages delivered by gavage were safe, effective and without adverse effects. Drug sequence of pazopanib switch to everolimus is the best among 4 combinations tested for primary tumor progression and lung metastasis for patient tumor KiCa-Pt58, P=0.0059 and P=0.008, respectively; while sunitinib switch to everolimus is the best sequence among combinations tested for primary tumor progress for patient tumor KiCa-Pt118, P=0.0116.
Conclusions: Combination chemotherapies may prove to be advantageous for treating RCCs. When used alternatively, more favorable results were seen in regards to primary tumor growth and distant organ metastasis. Our results to date indicate that our PDOX model can be used to identify specific targeted and individualized therapeutic strategies, and that each RCC patient tumor cells responded to targeted treatment differently. Thus, individualized therapeutic strategies are required for RCC patients; An Avatar approach can effectively assist personalized therapy in RCC.
Source of Funding: Ochsner Health System