Renal cell carcinoma avatar mouse models for the personalized cancer therapy era.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e15627-e15627
Author(s):  
Cristina Suarez ◽  
Mar Martinez ◽  
Enrique Trilla ◽  
Gabriela Jimenez-Valerio ◽  
Ines de Torres ◽  
...  
2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 551-551 ◽  
Author(s):  
Cristina Suarez ◽  
Mar Martinez ◽  
Enrique Trilla ◽  
Gabriela Jimenez-Valerio ◽  
Ines de Torres ◽  
...  

551 Background: Anti-angiogenic (AA) drugs are the cornerstone of first-line (FL) treatment in renal cell carcinoma (RCC). While several mechanisms of resistance to AA have been described, second line (SL) therapies are disappointing with short PFS reported. A recent strategy makes use of individual patient-derived tumor models in animals for drug testing simultaneously with that patient’s FL and SL treatments (AVATARs). The predictive value of each specific AVATAR for that same original patient will be key in order to predict SL treatment response in the clinic trying to help in decision making in this setting. Methods: We generated a unique panel of patient-derived mouse models of RCC based on the orthotopic implantation of primary renal tumor biopsies or metastasis directly obtained from patients. Sunitinib FL treatment followed by different SL treatments are evaluated in each mouse model. Response to treatments in these models and molecular profiling in search of predictive factors of response/resistance will be performed. Results: In this subset of 12 advanced RCC patients, tumor take rate in mice to develop AVATARs was 75% at 5 months after implantation. Previous data demonstrated a positive association of grafting capacity with tumor stage and Fuhrman grade (p < 0.0001). AVATAR models faithfully reproduced each patient’s histological characteristics and metastatic capacity. Time to tumor growth in AVATAR models significantly correlated to clinical outcome in each patient (spearman correlation, p < 0.0001). These advanced AVATAR models are treated FL with AA drugs and, at the moment of emergence of resistance to therapy, treatment is switched to known and experimental SL treatments in different animal cohorts. Updated results on AVATAR treatment and prediction of patient’s responses will be presented. Conclusions: Thorough characterization of these AVATAR models together with their response to AA treatments we will be able to predict response/resistance to new SL treatments for our RCC patients as a personalized cancer therapy approach.


2019 ◽  
Vol 50 (1) ◽  
pp. S10-S11 ◽  
Author(s):  
Nadia Benabdallah ◽  
Catherine Sai-Maurel ◽  
Didier Franck ◽  
Claire de Labriolle-Vaylet ◽  
Aurélie Desbrée ◽  
...  

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jie Wu ◽  
Tingting Liu ◽  
Lulu Sun ◽  
Shaojin Zhang ◽  
Gang Dong

Abstract Background Long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of human cancers, including renal cell carcinoma (RCC). Small nucleolar RNA host gene 4 (SNHG4) is reported to play an essential role in tumor growth and progression. However, the molecular mechanisms and function of SNHG4 in RCC remain undocumented. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine expression levels of SNHG4 in RCC tissue samples and cell lines. Cell counting kit-8, western blotting, activities of caspase-3, -8, and -9, wound-healing, and transwell invasion assays were performed to explore cell proliferation, apoptosis, migration, and invasion. The interaction among SNHG4, miR-204-5p, and RUNX2 was verified by bioinformatic analysis, a luciferase gene report, qRT-PCR, western blot analysis, and RNA immunoprecipitation assays. Xenograft mouse models were carried out to examine the role of SNHG4 in RCC in vivo. Results SNHG4 was highly expressed in RCC tissue samples and cell lines, and its upregulation was significantly involved in node involvement, distant metastasis, and reduced overall and relapse-free survival of patients with RCC. SNHG4 acted as an oncogenic lncRNA with promoted RCC cell proliferation, migration, invasion, and inhibited apoptosis. SNHG4 boosted tumor growth in xenograft mouse models. Mechanistically, SNHG4 functioned as a competing endogenous RNA (ceRNA) for sponging miR-204-5p, leading to the upregulation of its target RUNX2 to promote RCC cell proliferation and invasion. Conclusion SNHG4 and miR-204-5p might be indicated in RCC progression via RUNX2, suggesting the potential use of SNHG4/miR-204-5p/RUNX2 axis in RCC treatment.


2018 ◽  
Author(s):  
M Henjakovic ◽  
M Cherviakova ◽  
J Schleifenbaum ◽  
A Euteneuer ◽  
N Mikhael ◽  
...  

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