Modeling clear cell renal cell carcinoma and therapeutic implications

Abstract

Renal cell carcinoma (RCC) comprises a diverse group of malignancies arising from the nephron. The most prevalent type, clear cell renal cell carcinoma (ccRCC), is characterized by genetic mutations in factors governing the hypoxia signaling pathway, resulting in metabolic dysregulation, heightened angiogenesis, intratumoral heterogeneity, and deleterious tumor microenvironmental (TME) crosstalk. Identification of specific genetic variances has led to therapeutic innovation and improved survival for patients with ccRCC. Current barriers to effective long-term therapeutic success highlight the need for continued drug development using improved modeling systems. ccRCC preclinical models can be grouped into three broad categories: cell line, mouse, and 3D models. Yet, the breadth of important unanswered questions in ccRCC research far exceeds the accessibility of model systems capable of carrying them out. Accordingly, we review the strengths, weaknesses, and therapeutic implications of each model system that are relied upon today.

RETRACTED: Oncogenic miR-27a delivered by exosomes binds to SFRP1 and promotes angiogenesis in renal clear cell carcinoma

“… 3 Evidence exists demonstrating that RCCC leads to metabolic disorders and boosted angiogenesis, and therefore characterization of potential tumorigenesis-related molecules may contribute to innovated treatment options. 4 It is interesting that therapeutic strategies to combat angiogenesis have been widely proposed in variable malignancies, especially in the context of RCC. 5 However, the understanding of mechanisms behind signaling pathways orchestrating tumor angiogenesis in RCCC should be thoroughly probed.…”

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

“…Renal cell carcinoma (RCC) accounts for approximately 90% of all renal tumors and is derived from epithelial cells in renal tubules [ 2 , 3 ]. There are 3 primary histologic subtypes of RCC: clear cell RCC (ccRCC) (about 75–80% of RCC), papillary RCC (pRCC) (about 10%), and chromophobe RCC (chRCC) (about 5%) [ 4 , 5 ]. Rapid development in the molecular characterization of ccRCC has facilitated advances in targeted therapy, thus improving median survival of patients with advanced-stage RCC stage from less than 10 months before 2004 to 30 months by 2011 [ 6 ].…”

Exploiting the circuit breaker cancer evolution model in human clear cell renal cell carcinoma

“…Unlike many cancers that originate from gain-of-function mutations in OGs such as EGFR and RAS , ccRCC manifests with prevalent loss-of-function mutations in TSGs, making the development of predictive biomarkers for individual targeted therapies and/or immunotherapies extremely challenging. Nevertheless, new therapeutic modalities, novel genetically engineered mouse models, clinically relevant patient-derived cell line/xenograft models, and outcome-based biomarker studies altogether have begun to shed light on how these seemingly distinct research areas are in fact exquisitely interconnected [ 43 ]. Here, we wish to update essential findings in ccRCC, and present a novel concept of “Interconnected OG-TSG Circuit Breaker Cancer Evolution Model in ccRCC”.…”