Integration of Tumor Microenvironment in Patient-Derived Organoid Models Help Define Precision Medicine of Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) is a common urological tumor, with a poor prognosis, as the result of insensitivity to chemotherapy and radiotherapy. About 20%–30% of patients with RCC have metastasis at the first diagnosis, so only systemic treatment is possible. Due to the heterogeneity of renal tumors, responses to drugs differ from person to person. Consequently, patient-derived organoid, highly recapitulating tumor heterogeneity, becomes a promising model for high-throughput ex vivo drug screening and thus guides the drug choice of patients with RCC. Systemic treatment of RCC mainly targets the tumor microenvironment, including neovasculature and immune cells. We reviewed several methods with which patient-derived organoid models mimic the heterogeneity of not only tumor epithelium but also the tumor microenvironment. We further discuss some new aspects of the development of patient-derived organoids, preserving in vivo conditions in patients with RCC.

Diagnostic, predictive and prognostic molecular biomarkers in clear cell renal cell carcinoma: A retrospective study

“…The emergence of TKIs like Belzutifan and monoclonal antibodies such as bevacizumab has significantly enhanced patient survival and prognosis. 59 , 60 , 61 , 62 Despite VHL's critical role in the molecular pathogenesis of ccRCC, its exact prognostic and predictive implications remain uncertain. A recent meta‐analysis, however, suggests that VHL gene alterations appear to lack prognostic and predictive value for patients with ccRCC.…”

Current Limitations And The Future Promise Of Stem Cell-Derived Organoids In Renal Cell Carcinoma Treatment

“…Advances in PDOs during the last two decades has shed light on the precision medicine of RCC as PDOs can serve as a model preserving the majority of the patients' tumors' characteristics to predict the drug response of specific individuals [44] (Figure 6). Fatehullah et al [37] achieved a breakthrough in the field of regenerative medicine with the successful production of mesoderm-derived organoids.…”

Patient-derived organoids potentiate precision medicine in advanced clear cell renal cell carcinoma

“… 13–15 Nevertheless, the conventional PDO model with only spheroid tumor epithelium fails to preserve tumor microenvironment (TME) and thus has limited application in RCC. 16 Fortunately, a novel culture system of PDO based on air-liquid interface (ALI) has been reported to recapitulate both heterogeneity and architecture of TME, 17 which provides new prospects for establishment of reliable preclinical model to predict responses to immunotherapy in patients with RCC.…”