{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE315nnn/GSE315796/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE315796"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell RNAseq of from murine pancreas tumor (FPC)","description":"Oncogenic KRAS drives pancreatic ductal adenocarcinoma (PDAC), yet resistance to RAS antagonists limits benefit. We deployed two complementary preclinical PDAC models, including a degron-regulated KRASG12D-dependent transplantation model, and a KrasG12V-driven PDAC mouse model treated with the RAS(ON) multi-selective inhibitor, RMC-7977, to describe therapeutic response and resistance mechanisms. KRASG12D degradation provoked RAS-dependent relapse, characterized by compensatory wild-type (WT) RAS upregulation, restored MAPK signaling and proliferation, and a shift towards hybrid cancer cell states. RMC-7977 treatment triggered rapid RAS-independent resistance within 7 days, distinguished by suppressed MAPK yet restored proliferation with increased epithelial differentiation, and upregulation of Fyn. Antagonists of WT RAS or FYN attenuated resistance; and combining FYN antagonism with RMC-7977 prevented the uncoupling of MAPK signaling from cell proliferation in the respective KrasG12V PDAC model. Our findings identify distinct adaptive pathways orchestrating RAS-dependent versus RAS-independent resistance in PDAC and propose combination strategies for clinical evaluation to enhance KRAS-directed therapy durability.","dates":{"publication":"2026/09/07"},"accession":"GSE315796","cross_references":{"GSM":["GSM9437630","GSM9437631","GSM9437632","GSM9437633","GSM9437627","GSM9437628","GSM9437629"],"GPL":["30172"],"GSE":["315796"],"taxon":["Mus musculus"]}}