TY - JOUR
T1 - Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma
T2 - Suggestions from bench to bedside
AU - Santoni, Matteo
AU - Santini, Daniele
AU - Massari, Francesco
AU - Conti, Alessandro
AU - Iacovelli, Roberto
AU - Burattini, Luciano
AU - Tortora, Giampaolo
AU - Falconi, Massimo
AU - Montironi, Rodolfo
AU - Cascinu, Stefano
PY - 2014
Y1 - 2014
N2 - Metastatic disease occurs in a significant percentage of patients with renal cell carcinoma (RCC) and is usually associated with an overall poor prognosis. However, not all of the sites of metastases seem to have the same prognostic significance in patients receiving targeted agents. Indeed, patients with lung-only metastases seem to present a better survival than patients with other sites, whereas liver and bone metastases are associated with a worst prognosis. Some clinical studies suggest that metastatic sites are more responsive than primary tumors. This event may be due to intratumor heterogeneity in terms of somatic mutations, chromosome aberrations, and tumor gene expression, primarily centered around Von Hippel-Lindau (VHL) pathway, such as VHL mutations, HIF levels, vascular endothelial growth factor (VEGF) isoforms, and VEGF receptor levels. Nevertheless, these data do not completely explain the discordant biological behavior between primary tumor and metastatic sites. Understanding the causes of this discordance will have profound consequences on translational research and clinical trials in RCC. In this review, we overview current data on the differences between primary RCC and metastases in terms of drug target expression and clinical/radiological response to targeted agents, thus describing the prognostic role of different metastatic sites in RCC patients.
AB - Metastatic disease occurs in a significant percentage of patients with renal cell carcinoma (RCC) and is usually associated with an overall poor prognosis. However, not all of the sites of metastases seem to have the same prognostic significance in patients receiving targeted agents. Indeed, patients with lung-only metastases seem to present a better survival than patients with other sites, whereas liver and bone metastases are associated with a worst prognosis. Some clinical studies suggest that metastatic sites are more responsive than primary tumors. This event may be due to intratumor heterogeneity in terms of somatic mutations, chromosome aberrations, and tumor gene expression, primarily centered around Von Hippel-Lindau (VHL) pathway, such as VHL mutations, HIF levels, vascular endothelial growth factor (VEGF) isoforms, and VEGF receptor levels. Nevertheless, these data do not completely explain the discordant biological behavior between primary tumor and metastatic sites. Understanding the causes of this discordance will have profound consequences on translational research and clinical trials in RCC. In this review, we overview current data on the differences between primary RCC and metastases in terms of drug target expression and clinical/radiological response to targeted agents, thus describing the prognostic role of different metastatic sites in RCC patients.
KW - Metastatic sites
KW - Patient outcome
KW - Primary tumor
KW - Renal cell carcinoma
KW - Targeted therapy
KW - Tumor heterogeneity
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U2 - 10.1007/s10555-013-9453-5
DO - 10.1007/s10555-013-9453-5
M3 - Article
C2 - 24337954
AN - SCOPUS:84899921035
VL - 33
SP - 321
EP - 331
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
SN - 0167-7659
IS - 1
ER -