In this work, we evaluate the anti-tumor activity of two novel IGF-1R-targeting agents against renal cell carcinoma given alone or in combination with an mTOR inhibitor.
We identified six patients with metastatic RCC who initially responded to mTOR inhibitor therapy and then progressed, and had pre-treatment and post-treatment tumor samples available for analysis.
The identification of vascular endothelial growth factor (VEGF), its related receptor (VEGFR), and the mammalian target of rapamycin as dysregulated signaling pathways in the development and progression of RCC has resulted in the rational development of pharmaceutical agents capable of specifically targeting key steps in these pathways.
There has been a recent expansion of therapeutic options in metastatic renal cell carcinoma (RCC) targeted at the vascular endothelial growth factor and mammalian target of rapamycin pathways, which are fundamental to the biology of RCC.
The mechanistic target of rapamycin (mTOR) inhibitors, everolimus and temsirolimus, have widened therapeutic options to treat renal cell carcinoma (RCC).
The objective of this study was to investigate whether the activity of the mTOR inhibitor temsirolimus against RCC could be enhanced by OGX-011, an antisense oligodeoxynucleotide (ODN) targeting the stress-activated chaperone clusterin.
Collectively, these results demonstrate for the first time, to our knowledge, that deregulation of miR-99a is involved in the etiology of RCC partially via direct targeting mTOR pathway, which suggests that miR-99a may offer an attractive new target for diagnostic and therapeutic intervention in RCC.
These targeted approaches for RCC are based primarily on antiangiogenesis and/or specific kinase inhibitors targeting the vascular-endothelial growth factor and platelet-derived growth factor receptors, Raf and mammalian target of rapamycin inhibitor.
We report the largest retrospective cohort of patients with mChRCC treated with TT and no significant difference between AA and mTOR inhibitors was observed for TTF and OS.
It has recently been approved by the European Medicines Agency (EMA) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mammalian target of rapamycin (mTOR) pathway inhibitor-naive, following disease progression after one prior treatment with cytokine therapy for advanced RCC.
The relevant literature was reviewed concerning pathways implicated in the pathophysiology of renal cell carcinoma including pathways activated secondary to von Hippel-Lindau gene inactivation and PI-3 kinase/Akt/mammalian target of rapamycin pathway activation.
GSK-3β could directly phosphorylate 4EBP1 and activate the mTORC1 downstream signaling cascades to enhance protein biosynthesis and cell proliferation in RCC cell lines independent of rapamycin sensitivity.
Mammalian target of rapamycin (mTOR) inhibitors have anti-tumor effects against renal cell carcinoma, pancreatic neuroendocrine cancer and breast cancer.
Currently, targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors are widely used in the treatment of metastatic RCC.
Agents targeting the vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), as well as the mammalian target of rapamycin (mTOR) and immune checkpoint receptor programmed death 1 (PD-1) signaling pathway have improved clinical outcomes for patients with advanced renal cell carcinoma (RCC).
The objective of this study was to characterise the mechanism underlying acquired resistance to temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), in renal cell carcinoma (RCC).
Of the 8 polymorphisms, after adjusting for multiple comparisons, we found a significant association between one variant (rs2295080) in the promoter of MTOR and reduced RCC risk (P = 0.005, OR = 0.74, 95%CI = 0.59-0.91, TG/GG vs. TT).