A significant early discovery in RCC was frequent inactivation of the Von Hippel Lindau gene in ccRCC, which ultimately led to the development of vascular endothelial growth factor and mammalian target of rapamycin inhibitors.
From the standpoint of systemic therapy, more than a decade of using VEGF and mTOR inhibitors showed that they generally had limited efficacy in non-clear cell RCCs compared with clear cell RCCs.
The patients with nccRCC who had received vascular endothelial growth factor-targeted therapy had shorter PFS compared with that of ccRCC patients (median, 6.1 vs. 8.5 months; HR, 1.49; P < .001) but similar PFS when treated with mammalian target of rapamycin inhibitors (median, 4.3 vs. 4.4 months; HR, 0.92; P = .63).
We monitored the serum level of sIL-2R over time and examined phosphorylated Akt expression by the primary tumor in 47 patients with metastatic clear cell RCC (ccRCC) undergoing cytoreductive nephrectomy followed by first-line adjuvant therapy with IFN-alpha plus sequential VEGF-targeting therapy as second- or third-line adjuvant therapy.
Often Vascular Endothelial growth Factor (VEGF) and Mammalian Target of Rapamycin (mTOR) inhibitors are used, extrapolating the data from use of these agents in clear cell RCC.
We genotyped 16 key SNPs in 10 genes involved in sunitinib pharmacokinetics, pharmacodynamics and VEGF-independent angiogenesis in patients with metastatic clear-cell RCC treated with sunitinib as the first-line targeted therapy.
Total VEGF protein levels were quantified by enzyme-linked immunosorbent assay (ELISA) in tumor tissue samples from surgical specimens of 65 patients with clear cell RCC.
Our results confirm former communications regarding the association between SNPs in ABCB1, NR1/2, NR1/3 and VEGFR3 and sunitinib outcome in clear-cell RCC.
The molecular mechanisms involved in pRCC development and drug resistance are more diverse than in clear-cell RCC, in which inactivation of VHL occurs in the majority of tumours.
The results for 3p deletion, VHL gene mutation or VHL gene promoter region hypermethylation testing, along with the diffuse CD10-positivity in 2 cases confirmed 21 cases as clear cell papillary RCC (CCPRCC; CK7+, CA9+; no 3p loss, no VHL abnormality) and 10 cases as clear cell RCC (CCRCC; CK7+, CA9+; no 3p loss, VHL abnormality mutation/hypermethylation present).
Since ccRCC tumors with PBRM1 mutations respond to targeted therapy differently than tumors with BAP1 mutations, we focused on ccRCC-specific edges associated with tumors that exhibit alternate mutation profiles: VHL-PBRM1 or VHL-BAP1.
Because of an association between Von Hippel-Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years.
While mutations of SETD2, KDM5C, and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016) and PBRM1 (P = .017) were significantly more common among solid clear cell RCC.