Upregulation of the PI3K pathway has been implicated in the initiation and progression of several types of cancer, including renal cell carcinoma (RCC).
The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin 1 (mTORC1) signaling pathway is aberrantly activated in renal cell carcinoma (RCC).
Using specific inhibitors of phosphoinositide 3-kinase (PI3K) and depletion of Akt kinase by RNA interference, we established that PTHrP is one of the main factor involved in the constitutive activation of this pathway in human RCC, independently of von Hippel-Lindau (VHL) tumor suppressor gene expression.
Overall, miR‑205‑5p functions as a tumor suppressor in RCC by targeting VEGFA and the PI3K/Akt signaling pathway, providing a potential therapeutic target for the treatment of ccRCC.
This study proposes a novel treatment paradigm where combining PI3K/AKT/mTOR pathway inhibitors and autophagy inhibitors lead to enhanced RCC cell apoptosis.
The results showed that downregulation of the tumor suppressor gene PTEN expression and the inhibition of PTEN/PI3K/AKT cell signaling pathway may be involved in the occurrence and development of RCC in children.
Together, our results suggest that concurrent blockage of BRD4 and PI3K-AKT signalings by SF2523 efficiently inhibits RCC cell growth <i>in vitro</i> and <i>in vivo</i>.
We genotyped 70 genes involved in the pathogenesis of renal-cell carcinoma (including the VHL/HIF/VEGF and PI3K/AKT/mTOR pathways, and genes involved in immune regulation and metabolism) for single nucleotide polymorphisms.
Together, our study reveals a novel mechanism of PI3K-AKT inhibition-mediated feedback regulation and may identify FoxO as a novel biomarker to stratify patients with RCC for PI3K or AKT inhibitor treatment, or a novel therapeutic target to synergize with PI3K-AKT inhibition in RCC treatment.
A novel HDAC inhibitor OBP-801 and a PI3K inhibitor LY294002 synergistically induce apoptosis via the suppression of survivin and XIAP in renal cell carcinoma.
The optimal silencing si-RNA was subsequently selected and RCC cell lines 786-O and A498 were selected and transfected with either a si-PDK1 or activator of the PI3K-PDK1-Akt pathway for grouping purposes.
The PI3K/Akt pathway and other pathways associated with cyclins, DNA replication and cell cycle/mitotic regulation were also associated with the synergy of DAC and PTX against RCC.
The outlook for patients with advanced renal cell cancer (RCC) has been improved by targeted agents including inhibitors of the PI3 kinase (PI3K)-AKT-mTOR axis, although treatment resistance is a major problem.
The addition of LDL cholesterol increases activation of PI3K/AKT signalling and compromises the antitumour efficacy of TKIs against RCC and endothelial cells.
Among 184 everolimus-treated patients with RCC with NGS data, mutation rates in genes of interest were 6% (<i>TSC1</i>), 4.4% (<i>TSC2</i>), and 8.2% (<i>mTOR</i>); 44% harbored alterations in ≥1 PI3K pathway component.
Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention.
Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways).