Tumor explant animal model: Aiming towards tailor-made therapy of RCC

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At present, there is no means of predicting the response of an individual patient to a given drug, invariably some patients will respond whereas others will fail to respond and will experience adverse drug reactions. We propose a new model of “tailor-made chemotherapy” aimed at predicting the right treatment protocol for an individual patient. To accomplish this we have selected renal cell carcinoma (RCC) as a target for this form of personalized medicine, as advances in chemotherapy have introduced battery receptor tyrosine kinase (RTK) and mTOR inhibitors that provide promising treatment options that include Sorafenib, Sunitinib, Temsirolimus and Bevacizumab. This model involves transplanting and establishing fragments from a patients’ resected tumor into athymic mice, followed by treatment and response evaluation.
 Angiogenesis is necessary for the repair, development, and subsequent therapy of the tumor explants. Therefore, our first objective entails establishing the viabililty and angiogenicity of transplanted tumor samples. Fresh surgically resected clear cell renal carcinoma was collected and nine multiple fragments were prepared and transplanted subcutaneously into the backs of athymic nude mice. We examined the implantation potential of the tumors and evaluated tumor histology and cell proliferation and angiogenesis at 10, 20 and 30 days after transplantation.
 All tumor samples remained viable up to day 30 with only some exhibiting focal necrotic change. Initial histology results revealed some cell degradation at day 10, however, recovery process was from day 20 and continued until 30 days after implantation. Proliferation rates determined by PCNA immunohistochemistry were 25.8%, 15.4%, and 42.7%, at 10-day, 20-day, and 30 day after tumor explants, respectively, compared to 31.2% of the original tumor sample. Micro vessel density analysis with von Willebrand factor and CD31 showed fairly same trend expressions between the original tumor sample and the 30-day tumor explant tumors.This model presents a new plattform in the development of personalized medicine and angiogenesis models. Future experiments to evaluate treatment response using the explant tumor model, to predict the best treatment option for the individual patient, need to be conducted to to further validate its utility in the clinical setting.