@article{3f99661af2de469397916265bef9a695,
title = "Whole-exome sequencing in two extreme phenotypes of response to VEGF-targeted therapies in patients with metastatic clear cell renal cell carcinoma",
abstract = "Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC). Patients with mRCC who had received first-line sunitinib or pazopanib and were in 2 extreme phenotypes of response were identified. Extreme responders (ERs) were defined as those with partial response or complete response for 3 or more years (n=13) and primary refractory patients (PRPs) were defined as those with progressive disease within the first 3 months of therapy (n=14). International Metastatic RCC Database Consortium prognostic scores were not significantly different between the groups (P=.67). Considering the genes known to be mutated in RCC at significant frequency, PBRM1 mutations were identified in 7 ERs (54%) versus 1 PRP (7%) (P=.01). In addition, mutations in TP53 (n=4) were found only in PRPs (P=.09). Our data suggest that mutations in some genes in RCC may impact response to VEGF-TT.",
author = "Fay, {Andre P.} and {De Velasco}, Guillermo and Ho, {Thai H.} and {Van Allen}, {Eliezer M.} and Bradley Murray and Laurence Albiges and Sabina Signoretti and Hakimi, {A. Ari} and Stanton, {Melissa L.} and Joaquim Bellmunt and McDermott, {David F.} and Atkins, {Michael B.} and Garraway, {Levi A.} and Kwiatkowski, {David J.} and Choueiri, {Toni K.}",
note = "Funding Information: Dr. de Velasco has disclosed that his spouse receives salary from GlaxoSmithKline. Dr. Van Allen has disclosed that he receives consulting fees from or is a scientific advisor for Roche Ventana and Syapse. Dr. Albiges has disclosed that she is a scientific advisor for Novartis, Pfizer, Bayer, Sanofi, and Amgen, and receives research support from Novartis and Pfizer. Dr. Bellmunt has disclosed that he receives consulting fees from or is a scientific advisor for Astellas Pharma, Pfizer, and Pierre-Fabre; receives research support from Millennium and Sanofi; and has received compensation for travel, accommodations, expenses from MSD Oncology and Pfizer. Dr. McDermott has disclosed that he is on the data safety monitoring board for Pfizer; is a consultant for Bristol-Myers Squibb, Genentech BioOncology, Merck, Pfizer, Novartis, Eisai, Excelixis, and Array BioPharm; and receives research support from Prometheus. Dr. Atkins has disclosed that he receives consulting fees from or is a scientific advisor for Novartis, Pfizer, Genentech, Bristol-Myers Squibb, Merck, and GlaxoSmithKline. Dr. Garraway has disclosed that he receives consulting fees from and has equity interest in Foundation Medicine. Dr. Kwiatkowski has disclosed that he receives consulting fees from Novartis. Dr. Choueiri has disclosed that he receives institutional funding from Bristol-Myers Squibb, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, and TRACON Pharma, and is a scientific advisor for Bayer, GlaxoSmithKline, Merck, Novartis, and Pfizer. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. This work was supported by the Trust family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer Research (to Dr. Choueiri) at Dana-Farber Cancer Institute, the Dana-Farber/Harvard Cancer Center Kidney Cancer Program, the Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE P50 CA101942-01, and by a grant from the Kidney Cancer Association. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher Copyright: {\textcopyright} JNCCN - Journal of the National Comprehensive Cancer Network. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2016",
month = jul,
day = "1",
doi = "10.6004/jnccn.2016.0086",
language = "English (US)",
volume = "14",
pages = "820--824",
journal = "JNCCN Journal of the National Comprehensive Cancer Network",
issn = "1540-1405",
publisher = "Cold Spring Publishing LLC",
number = "7",
}