Mus musculus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA339310 | ENA |
REPOSITORIES: ENA
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Project description:We have examined the microRNA expression in 154 lung adenocarcinoma samples and 20 paired normal lung tissue samples and investigated the microRNA expression to clinical variables, EGFR- and KRAS- mutational status and time to progression. 174 samples are analyzed. 154 from lung adenocarcinoma tumor tissue and 20 from paired normal lung tissue samples. No replicates or control samples included.
2014-03-10 | E-GEOD-48414 | biostudies-arrayexpress
Project description:We have examined the microRNA expression in 154 lung adenocarcinoma samples and 20 paired normal lung tissue samples and investigated the microRNA expression to clinical variables, EGFR- and KRAS- mutational status and time to progression.
2014-03-10 | GSE48414 | GEO
Project description:Label-free whole cell proteomics was performed for the following cell lines: LHS-PREC engineered to overexpress MYC or EV; P4936 overexpressing MYC on a tetracycline-repressible promotor; MCF10A cells expressing signal transduction oncogenes AKT, BRAF, EGFR, HER2, KRAS, MEK; KP4 and PSN1 PDAC cell lines vs HPDE normal pancreatic cell; PDX-derived osteosarcoma cell lines with MYC amplification vs hFOB cell
2022-08-11 | PXD033373 | Pride
Project description:Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS, we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models, including human and murine cell lines, patient-derived organoids, human PDAC explants, subcutaneous and orthotopic cell-line or patient-derived xenografts, syngeneic allografts, and genetically engineered mouse models. We observed broad and pronounced anti-tumor activity across these models following direct RAS inhibition at doses and concentrations that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS inhibition in the setting of PDAC.
2024-03-15 | PXD047878 | Pride
Project description:The aim of the study was to investigate gene expression tumour progression of KRas*/MYC driven lung tumours from adenocarcinoma in situ to invasive disease.
2018-06-01 | E-MTAB-6432 | biostudies-arrayexpress
Project description:Cancer genome sequencing has uncovered substantial complexity in the mutational landscape of tumors. Given this complexity, experimental approaches are necessary to establish the impact of combinations of genetic alterations on tumor biology and to uncover genotype-dependent effects on drug sensitivity. In lung adenocarcinoma, EGFR mutations co-occur with many putative tumor suppressor gene alterations, however the extent to which these alterations contribute to tumor growth and their response to therapy in vivo has not been explored experimentally. By integrating a novel mouse model of oncogenic EGFR-driven Trp53-deficient lung adenocarcinoma with multiplexed CRISPR–Cas9-mediated genome editing and tumor barcode sequencing, we quantified the effects of inactivation of ten putative tumor suppressor genes. Inactivation of Apc, Rb1, or Rbm10 most strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2 – which were the strongest drivers of tumor growth in an oncogenic Kras-driven model – reduced EGFR-driven tumors growth. These results were consistent with the relative frequency of these tumor suppressor gene alterations in human EGFR and KRAS-driven lung adenocarcinomas. Furthermore, Keap1 inactivation reduced the sensitivity of tumors to osimertinib in the EGFRL858R;p53flox/flox model. Importantly, in human EGFR/TP53 mutant lung adenocarcinomas, mutations in the KEAP1 pathway correlated with decreased time on tyrosine kinase inhibitor treatment. Our study highlights how genetic alterations can have dramatically different biological consequences depending on the oncogenic context and that the fitness landscape can shift upon drug treatment.
2021-02-01 | GSE146550 | GEO
Project description:We aimed to decipher human APOBEC3A driven mutational differences in pancreatic tumor in vivo using a genetically engineered mouse model of pancreatic cancer. Murine pancreatic tumor formation was driven by p53fl/+;KrasLSL-G12D/+;Pdx1-Cre;Rosa26LSL-YFP (PKCY) and p53fl/+;KrasLSL-G12D/+;Pdx1-Cre; Rosa26LSL-YFP; A3A+/- (A3A PKCY).
2021-09-06 | E-MTAB-9972 | biostudies-arrayexpress
Project description:Lung adenocarcinoma (LUAD), commonly driven by KRAS mutations, is responsible for 7% of all cancer mortality. The first allele-specific KRAS inhibitors were recently approved in LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, and patient samples we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing Kras induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Our results uncover an unexpected role for KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar differentiation may augment KRAS-targeted therapies in LUAD.
2023-11-01 | GSE246481 | GEO
Project description:Lung adenocarcinoma (LUAD), commonly driven by KRAS mutations, is responsible for 7% of all cancer mortality. The first allele-specific KRAS inhibitors were recently approved in LUAD, but clinical benefit is limited by intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative alveolar stem cells by self-renewing and replacing alveolar type 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, and patient samples we found inhibition of KRAS promotes transition to a quiescent AT1-like cancer cell state in LUAD tumors. Similarly, suppressing Kras induced AT1 differentiation of wild-type AT2 cells upon lung injury. The AT1-like LUAD cells exhibited high growth and differentiation potential upon treatment cessation, whereas ablation of the AT1-like cells robustly improved treatment response to KRAS inhibitors. Our results uncover an unexpected role for KRAS in promoting intra-tumoral heterogeneity and suggest targeting alveolar differentiation may augment KRAS-targeted therapies in LUAD.
2023-11-01 | GSE246480 | GEO
Project description:Mutational landscape in genetically engineered, carcinogen-induced, and radiation-associated mouse models of sarcoma
| PRJNA516973 | ENA