scholarly journals Genomic Alterations and Outcomes with VEGF-Targeted Therapy in Patients with Clear Cell Renal Cell Carcinoma

Kidney Cancer ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 49-56 ◽  
Author(s):  
M.I. Carlo ◽  
B. Manley ◽  
S. Patil ◽  
K.M. Woo ◽  
D.T. Coskey ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Genomic Alterations ◽  
Cell Renal Cell Carcinoma

617 GENOMIC ALTERATIONS ASSOCIATED WITH METASTASIS AND POOR PROGNOSIS IN CLEAR CELL RENAL CELL CARCINOMA

2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Jimsgene Sanjmyatav ◽  
Carsten Schwaenen ◽  
Sven Wessendorf ◽  
Markus Kreuz ◽  
Thomas Steiner ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Genomic Alterations ◽  
Cell Renal Cell Carcinoma

Proteomic stratification of clear cell renal cell carcinoma utilizing The Cancer Genome Atlas (TCGA) with external validation.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 406-406
Author(s):  
Samuel D. Kaffenberger ◽  
Giovanni Ciriello ◽  
Andrew G. Winer ◽  
Martin Henner Voss ◽  
Jodi Kathleen Maranchie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
External Validation ◽  
Mtor Pathway ◽  
The Cancer Genome Atlas ◽  
Genomic Alterations ◽  
Cell Renal Cell Carcinoma ◽  
Cluster 2

406 Background: Proteomics represents the ultimate convergence of DNA and expression alterations. We therefore sought to leverage TCGA reverse phase protein array (RPPA) data with an independent proteomic platform to identify druggable targets and pathways associated with prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Unsupervised hierarchical consensus clustering was performed and differentially expressed proteins were identified for pathway analysis. Associations with clinicogenomic factors were assessed and Cox proportional hazards models were performed for disease-specific survival (DSS). Results: RPPA clustering of 324 patients from the ccRCC TCGA revealed 5 robust clusters characterized by alterations in specific pathways and divergent prognoses. Cluster 1 was characterized by poor DSS, decreased expression of receptor tyrosine kinases (RTK) and upregulation of the mTOR pathway. It was also associated with mTOR pathway genomic alterations, sarcomatoid histology and the ccb prognostic mRNA signature (all p<0.001). Cluster 2 was characterized by increased expression of RTKs and interestingly, had upregulation of the mTOR pathway with excellent DSS. After accounting for stage and grade, cluster designation remained independently associated with DSS (HR 0.23 for cluster 2, 95% CI 0.08-0.68; p=0.008). External validation was performed on a separate cohort of 189 patients with a different quantitative proteomics platform. A panel of phosphoproteins (pHER1, pHER2, pHER3, pSHC, pMEK, pAKT), highly discriminant between the most divergent RPPA clusters (1 and 2) was evaluated. Those at the highest quartile of activation in > 3 proteins were associated with improved DSS (HR 0.19, 95% CI 0.05-0.082; p=0.03). Patients with mTOR pathway activation segregated to those with coincident RTK activation (n=83) and those without (n=13). Conclusions: We have identified and validated proteomic signatures which cluster ccRCC patients into 5 prognostic groups. Furthermore, two distinct mTOR-activated clusters—one with high RTK activity and one with increased mTOR pathway genomic alterations were revealed, which may have prognostic and therapeutic implications.

scholarly journals Efficacy of Neoadjuvant Targeted Therapy in Treatment of Patients with Localised Clear-Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
O. A. Voylenko ◽  
O. E. Stakhovsky ◽  
I. V. Vitruk ◽  
O. A. Kononenko ◽  
M. V. Pikul ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumour Size ◽  
Combined Treatment ◽  
Response Evaluation ◽  
Cell Renal Cell Carcinoma ◽  
Kidney Preservation

Aim. This study aimed to evaluate the efficacy of neoadjuvant targeted therapy (TT) in patients with localised clear-cell renal cell carcinoma (RCC). Materials and Methods. A special randomised trial was planned and conducted by the Research Department of Plastic and Reconstructive Oncology in the National Cancer Institute of Ukraine for testing the clinical efficacy of neoadjuvant TT in the treatment of clear-cell localised RCC, and the primary endpoint was tumour response evaluation after TT. The secondary endpoints included evaluation of dependence between the use of neoadjuvant TT and the probability of partial nephrectomy and the correlation between tumour size, stage, remaining functioning parenchyma volume, and response to systemic therapy. Results. Overall, 118 patients met the inclusion criteria and were randomly assigned to receive combined treatment or surgery alone. The percentage of tumour regression ranged from 0% to 60%, and the median was (95% confidence interval) 20.5 ± 14.3 (16.8–24.3%). Most of the patients had a slightly positive response to TT (3%–29% decrease in tumour size); n = 44 (76.9%) cases. Partial response by the Response Evaluation Criteria in Solid Tumours, version 1.1, was observed in 14 (24.1%) patients and reached a maximum of 60% regression. Tumour reduction in the neoadjuvant TT group allowed kidney preservation in 53 (91.4%) patients. In the control group, the number of organ-sparing procedures was significantly lower (n = 20, 33.3%). The statistical difference was relevant (x2 = 42.1; p < 0.001 ). Conclusion. The positive results of neoadjuvant TT obtained in our study indicate the clinical validity of combined treatment in patients with localised RCC.

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