Ex-Vivo Treatment of Tumor Tissue Slices as a Predictive Preclinical Method to Evaluate Targeted Therapies for Patients with Renal Carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is the third type of urologic cancer. At time of diagnosis, 30% of cases are metastatic with no effect of chemotherapy or radiotherapy. Current targeted therapies lead to a high rate of relapse and resistance after a short-term response. Thus, a major hurdle in the development and use of new treatments for ccRCC is the lack of good pre-clinical models that can accurately predict the efficacy of new drugs and allow the stratification of patients into the correct treatment regime. Here, we describe different 3D cultures models of ccRCC, emphasizing the feasibility and the advantage of ex-vivo treatment of fresh, surgically resected human tumor slice cultures of ccRCC as a robust preclinical model for identifying patient response to specific therapeutics. Moreover, this model based on precision-cut tissue slices enables histopathology measurements as tumor architecture is retained, including the spatial relationship between the tumor and tumor-infiltrating lymphocytes and the stromal components. Our data suggest that acute treatment of tumor tissue slices could represent a benchmark of further exploration as a companion diagnostic tool in ccRCC treatment and a model to develop new therapeutic drugs.

Immunotherapy in Renal Cell Carcinoma: The Future Is Now

“…The 3D culture models of ccRCC could represent good pre-clinical models based on tissue slices preserving the stromal components of the TME [88]. Already used for TKI targeted therapies, these models are increasingly being considered as potential platforms for monitoring immunotherapy responses [89].…”

Applying Tissue Slice Culture in Cancer Research—Insights from Preclinical Proton Radiotherapy

“…Preclinical cancer research relies on in vitro, in vivo, and ex vivo models, and their translational potential for the clinic. Thin-cut tissue slices have the advantage of a relatively fast and inexpensive cultivation with straightforward culture procedures, and the possibility to investigate cell interactions within the original 3D architecture [25]. Furthermore, it provides the opportunity to greatly reduce animal numbers in experiments [26].…”

“…Furthermore, it provides the opportunity to greatly reduce animal numbers in experiments [26]. Tumor and brain slice cultures have been successfully applied for drug screening [25,[27][28][29][30][31] and radiation experiments [28,30,31], but so far not in the context of PBRT. In this study, we described an experimental setup for proton irradiation of TSC and OBSC, and clinically evaluated the relevant endpoints regarding radiooncological research.…”

Modern Approaches to Testing Drug Sensitivity of Patients’ Tumors (Review)

“…Slices are sections or of tumor tissue samples, 300-500 µm thick, from the primary tumor and placed into a culture medium [73]. Cultured slices present well tumor micro-environment; the method used to derive them is rather easy and not time-consuming, and can be applied in most solid tumors [74][75][76]. When cultured up to 7 days, slices have been found to preserve tumor morphological properties [74].…”