Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, on H441 cells.

ABSTRACT: Transcriptional effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, on H441 cells.

PROVIDER: PRJNA1165230 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, on H441 cells.

Project description:Despite KRAS-G12V being the second most common KRAS mutation in cancer, there are no approved direct KRAS-G12V inhibitors. Difficulties with inhibiting oncogenes using conventional approaches have prompted the use of RNAi as a therapeutic approach. RNAi has faced numerous obstacles as a cancer therapeutic, including the lack of cancer-specific tissue targeting, rapid oligonucleotide nuclease degradation and clearance from the circulation. Recently, the use of targetable ligands conjugated to chemically modified siRNAs has shown remarkable promise in circumventing these barriers. We demonstrate that EFTX-G12V is highly selective for KRAS-G12V and has improved therapeutic activity over pan-KRAS targeting, including enhanced inhibition of several cancer hallmarks. With a novel RNAi delivery platform, we demonstrate tumor silencing of KRAS-G12V and significant anti-tumor activity across several cancer models. Our findings represent a technologic advance in oncogene targeting using RNAi and reveal new biologic insights in KRAS targeting that may have broad implications with regards to safety and efficacy. This dataset collects the RNA-Seq data for the H441 cell line.

2025-07-16 | GSE278018 | GEO

Transcriptional effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, on H727 cells.

2025-07-16 | GSE278019 | GEO

Characterization of off-target effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, in SKCO1 cells.

2025-07-16 | GSE278020 | GEO

Transcriptional effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, on H727 cells.

Project description:Transcriptional effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, on H727 cells.

| PRJNA1165234 | ENA

Characterization of off-target effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, in SKCO1 cells.

Project description:Characterization of off-target effects of a first-in-class EGFR-directed KRAS G12V selective inhibitor, EFTX-G12V, in SKCO1 cells.

| PRJNA1165231 | ENA

KRAS mutation (G12V) expression by pBABE-Puro vector in NCI-H1703 cells

Project description:The goal of this study was to determine genes affected by expressing KRAS mutation (G12V) in NCI-H1703 cells This data was used in Meng Wang et. al. Cancer Research 2016 to determine the alterations of gene expression profiling associated with expression of KRAS mutation (G12V). The experiment uses a pBABE-Puro vector encoding KRAS G12V and a corresponding empty vector control.

2016-03-23 | E-GEOD-79486 | biostudies-arrayexpress

Murine lung tumors- HER2(V659E) and KRAS(G12V) vs normal lung

Project description:Transcriptiional profling of 13 normal lung samples, 18 lung KRAS(G12V) tumor samples, and 18 lung HER2(V659E) tumor samples 13 normal lung samples, 18 lung KRAS(G12V) tumor samples, and 18 lung HER2(V659E) tumor samples hybridized against Stratagene universal mouse reference RNA with dye swap

2009-11-30 | E-GEOD-18784 | biostudies-arrayexpress

Whole exome sequencing of human tumours and cell lines to investigate how ERBB2 and KRAS Alterations mediate response to EGFR inhibitors in early stage Gallbladder Cancer

Project description:Purpose: The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. The development of new and effective treatment has been and continues to be a major public health imperative. Methods: We report mutational and copy number analysis of 44 predominantly early-staged gallbladder tumors and 5-gallbladder cancer cell lines by a combination of directed and whole exome sequencing at an average coverage of 100X and above. Using gallbladder cancer cell lines and xenograft mouse models we performed phospho-proteome array profiling, followed by an in-depth functional characterization. Results: We describe recurrent activating ERBB2 somatic mutation in 6 of 44 gallbladder primary tumors with an overall mutation frequency of 13%, along with KRAS activating mutations in 3 of 44 samples. Consistent with whole exome findings, a phospho-proteomic array profile of 49-tyrosine kinase revealed constitutive phosphorylation of ERBB2 and EGFR that were found to heterodimerize. We demonstrate that treatment with ERBB2-specific, EGFR-specific shRNA or with covalent EGFR family inhibitor BIBW-2992 inhibits transformation, survival, migration, invasion, and tumor forming characteristics of gallbladder cancer cells harboring wild type or KRAS (G13D) but not KRAS (G12V) mutation. Furthermore, we show in vivo reduction in tumor size is paralleled by a reduction in the amounts of phospho-ERK in KRAS (G13D) but not in KRAS (G12V) xenografts, validating the in vitro findings Conclusion: Findings from this study implicate ERBB2 as an important therapeutic target in early stage gallbladder cancer. We also present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.

2018-12-29 | E-MTAB-6619 | biostudies-arrayexpress

KRAS mutation (G12V) expression by pBABE-Puro vector in NCI-H1703 cells

2016-03-23 | GSE79486 | GEO

KRAS G12V digestion by 20S proteasome

Project description:KRAS is a well known tumor associated antigen. It’s a GTPase that functions as molecular switch in regulatory pathways responsible for proliferation and survival. It’s frequently mutated in a variety of cancers. One of the possible driver mutations is G12V substitution, which impairs KRAS GTPase activity and renders the mutants persistently in the GTP-bound active form, thereby promoting tumorigenesis and tumor malignancy. Its high frequency in cancers makes KRAS an attractive target for immunotherapy. We performed in vitro digestions of synthetic polypeptide corresponding to KRAS2-35 carrying the mutation with purified 20S proteasome. Samples were measured by LC-MS/MS.

2019-10-24 | PXD015580 | Pride

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