Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of KO-2806 and cabozantinib treatment on gene expression in KI-12-0073 clear cell renal cell carcinoma (ccRCC) xenografts

ABSTRACT: Anti-angiogenic tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor receptor (VEGFR) remain the backbone of therapy in advanced renal cell carcinoma (RCC). However, durability of responses is limited, and resistance typically arises. There is therefore a need for therapeutic agents that enhance responses to TKIs, including in patients who progress on prior TKI therapies. Here we show that the farnesyl transferase inhibitor (FTI) KO-2806 inhibits mTORC1 signaling in endothelial cells to enhance the antiangiogenic properties of TKIs. This activity correlates with tumor regressions and robust inhibition of tumor vasculature in preclinical models of clear cell RCC (ccRCC) exposed to the combination of anti-VEGFR TKIs and KO-2806. Additionally, the KO-2806 plus anti-VEGFR TKI combinations retain activity in tumors previously exposed to TKIs, suggesting potential benefit of KO-2806 as a combination partner across the treatment continuum in RCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294454 | GEO | 2026/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression changes during resistance toward vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma (RCC)

2015-05-21 | GSE64052 | GEO

KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

Project description:This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.

| 91122 | ecrin-mdr-crc

Gene expression changes during resistance toward vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma (RCC)

Project description:This study was performed to understand the gene expression changes that accompany treatment of renal cell carcinoma (RCC) with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Human RCC cell lines were implanted into the flanks of nude beige mice, allowed to reach 12mm in long axis, and then treated with TKIs (sunitinib or sorafenib). Tumors were excised at 2 timepoints (prior to any therapy and at the 20mm endpoint of the study) and gene expression analysis was performed. Sunitinb or sorafenib were administered to mice bearing either 786-O or A498 xenografts. Mice were sacrificed and tumors excised for RNA extraction at pretreatment size of 12mm, or at 20mm, the mandated maximum tumor size allowed at our institution.

2015-05-21 | E-GEOD-64052 | biostudies-arrayexpress

Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [bulk RNA-seq]

Project description:Vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors (VEGFR-TKIs) and aPD1 combinations are effective in multiple solid tumors, particularly in clear cell renal cell carcinoma (ccRCC), due it’s characteristic pseudo-hypoxic, hyper-angiogenic state driven by biallelic VHL-loss. However, long-term durability is inferior to dual aPD1/aCTLA4 regimens, yet the mechanisms underlying these differences remain unclear. Since tumor-associated macrophages (TAMs) are implicated in therapeutic resistance, we used scRNAseq to investigate TAM evolution following VEGFR-TKI, aPD1 and combined VEGFR-TKI/aPD1 treatment in a transgenic ccRCC mouse model. We identify hypoxia-responsive SPP1+ TAMs that are absent in baseline pseudo-hypoxic tumors. This proxy of true hypoxia tracks with successful response to VEGFR-TKI/aPD1 in mouse and human on-treatment samples, reflecting treatment-induced hypoxic necrosis. Paradoxically, pretreatment hypoxia predicted worse outcomes across multiple VEGFR-TKI/aPD1 trial and real-world cohorts and extended exposure to hypoxia-inducing VEGFR-TKIs and aPD1 exacerbated metastasis in mice, highlighting the dual implications of hypoxia in ccRCC disease trajectory.

2026-04-23 | GSE293952 | GEO

Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma

2026-04-23 | GSE293450 | GEO

Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [scRNAseq]

2026-04-23 | GSE294109 | GEO

Hypoxia shapes both therapeutic response and resistance in metastatic clear cell renal cell carcinoma [Spatial Transcriptomics]

2026-04-23 | GSE294006 | GEO

Identification of HGF/c-MET as a biomarker of resistance to Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors

Project description:Therapeutic resistance to VEGFR signaling inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the contribution of stromal and tumor cells to resistance of NSCLC to VEGFR tyrosine kinase inhibitors (TKIs). Gene expression analysis of stromal (mouse) and tumor (human) compartments enabled us to identify the HGF/c-MET pathway as a driver and a potential biomarker of VEGFR TKI resistance.

2017-07-06 | GSE64472 | GEO

Microarray expression profile of long noncoding RNAs in EGFR-TKI resistance of lung adenocarcinoma

Project description:Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, we generate EGFR-TKI-resistant HCC827-8-1 cells to be analyzed by microarray with their parental HCC827cells. gefitinib resistant HCC827-8-1 cells with three replications; gefitinib-sensitive HCC827 cells with three replications

2016-08-23 | E-GEOD-74575 | biostudies-arrayexpress

Establishment and characterization of six canine hepatocellular carcinoma cell lines (Transcriptional changes induced by drug treatment with toceranib or sorafenib)

Project description:Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

2024-05-20 | GSE267624 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data