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Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?

Renal cell carcinoma (RCC) with sarcomatoid differentiation belongs to the most aggressive clinicopathologic phenotypes of RCC. It is characterized by a high propensity for primary metastasis and limited therapeutic options due to its relative resistance to established systemic targeted therapy. Mos...

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Autores principales: Pichler, Renate, Compérat, Eva, Klatte, Tobias, Pichler, Martin, Loidl, Wolfgang, Lusuardi, Lukas, Schmidinger, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468799/
https://www.ncbi.nlm.nih.gov/pubmed/30934624
http://dx.doi.org/10.3390/cancers11030422
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author Pichler, Renate
Compérat, Eva
Klatte, Tobias
Pichler, Martin
Loidl, Wolfgang
Lusuardi, Lukas
Schmidinger, Manuela
author_facet Pichler, Renate
Compérat, Eva
Klatte, Tobias
Pichler, Martin
Loidl, Wolfgang
Lusuardi, Lukas
Schmidinger, Manuela
author_sort Pichler, Renate
collection PubMed
description Renal cell carcinoma (RCC) with sarcomatoid differentiation belongs to the most aggressive clinicopathologic phenotypes of RCC. It is characterized by a high propensity for primary metastasis and limited therapeutic options due to its relative resistance to established systemic targeted therapy. Most trials report on a poor median overall survival of 5 to 12 months. Sarcomatoid RCC can show the typical features of epithelial-mesenchymal transition (EMT) and may contain epithelial and mesenchymal features on both the morphological and immunhistochemical level. On the molecular level, next-generation sequencing confirmed differences in driver mutations between sarcomatoid RCC and non-sarcomatoid RCC. In contrast, mutational profiles within the epithelial and sarcomatoid components of sarcomatoid RCC were shown to be identical, with TP53 being the most frequently altered gene. These data suggest that both epithelial and sarcomatoid components of RCC originate from the same progenitor cell, segregating primarily according to the underlying histologic epithelial subtype of RCC (clear cell, papillary or chromophobe). Current studies have shown that sarcomatoid RCC express programmed death 1 (PD-1) and its ligand (PD-L1) at a much higher level than non-sarcomatoid RCC, suggesting that blockade of the PD-1/PD-L1 axis may be an attractive new therapeutic strategy. Preliminary results of clinical trials evaluating checkpoint inhibitors in patients with sarcomatoid RCC showed encouraging survival data and objective response and complete response rates of up to 62% and 18%, respectively. These findings may establish a new standard of care in the management of patients with sarcomatoid RCC.
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spelling pubmed-64687992019-04-24 Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope? Pichler, Renate Compérat, Eva Klatte, Tobias Pichler, Martin Loidl, Wolfgang Lusuardi, Lukas Schmidinger, Manuela Cancers (Basel) Commentary Renal cell carcinoma (RCC) with sarcomatoid differentiation belongs to the most aggressive clinicopathologic phenotypes of RCC. It is characterized by a high propensity for primary metastasis and limited therapeutic options due to its relative resistance to established systemic targeted therapy. Most trials report on a poor median overall survival of 5 to 12 months. Sarcomatoid RCC can show the typical features of epithelial-mesenchymal transition (EMT) and may contain epithelial and mesenchymal features on both the morphological and immunhistochemical level. On the molecular level, next-generation sequencing confirmed differences in driver mutations between sarcomatoid RCC and non-sarcomatoid RCC. In contrast, mutational profiles within the epithelial and sarcomatoid components of sarcomatoid RCC were shown to be identical, with TP53 being the most frequently altered gene. These data suggest that both epithelial and sarcomatoid components of RCC originate from the same progenitor cell, segregating primarily according to the underlying histologic epithelial subtype of RCC (clear cell, papillary or chromophobe). Current studies have shown that sarcomatoid RCC express programmed death 1 (PD-1) and its ligand (PD-L1) at a much higher level than non-sarcomatoid RCC, suggesting that blockade of the PD-1/PD-L1 axis may be an attractive new therapeutic strategy. Preliminary results of clinical trials evaluating checkpoint inhibitors in patients with sarcomatoid RCC showed encouraging survival data and objective response and complete response rates of up to 62% and 18%, respectively. These findings may establish a new standard of care in the management of patients with sarcomatoid RCC. MDPI 2019-03-25 /pmc/articles/PMC6468799/ /pubmed/30934624 http://dx.doi.org/10.3390/cancers11030422 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Commentary
Pichler, Renate
Compérat, Eva
Klatte, Tobias
Pichler, Martin
Loidl, Wolfgang
Lusuardi, Lukas
Schmidinger, Manuela
Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?
title Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?
title_full Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?
title_fullStr Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?
title_full_unstemmed Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?
title_short Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope?
title_sort renal cell carcinoma with sarcomatoid features: finally new therapeutic hope?
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468799/
https://www.ncbi.nlm.nih.gov/pubmed/30934624
http://dx.doi.org/10.3390/cancers11030422
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