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Gene expression profile at single cell level of Drug-tolerant persister cells induced by targeted therapy in lung adenocarcinoma.

ABSTRACT: Drug-tolerant persister (DTP) stage is viewed as a major source of non-genetic drug resistance. We use single cell RNA seq to reveal the transcriptomic heterogeniety of DTP stage

ORGANISM(S): Homo sapiens

PROVIDER: GSE275199 | GEO | 2025/05/14

REPOSITORIES: GEO

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Chromasome accessibility profiles at single cell level of Drug-tolerant persister cells induced by targeted therapy in lung adenocarcinoma.

Project description:Drug-tolerant persister (DTP) stage is viewed as a major source of non-genetic drug resistance. We use single cell ATAC seq to reveal the epigenetic heterogeniety of DTP stage

2025-05-14 | GSE275305 | GEO

Gene expression profiling of drug-tolerant persister PC9 non-small cell lung cancer cells derived from osimertinib treatment

Project description:Targeting drug tolerant persister (DTP) cells may present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. We sought to identify therapeutically exploitable vulnerabilities in DTP cells using the EGFR-mutant non-small cell lung cancer cell line PC9 as an experimental model. Here we provide RNAseq gene expression profiling data generated from parental PC9 cells compared to PC9 DTP cells generated from nine days of treatment with 2 uM osimertinib. These data can be used to identify genes and pathways which are upregulated in DTP cells, revealing potential therapeutic targets.

2020-06-25 | GSE153183 | GEO

The Ontogeny and Vulnerabilities of Lapatinib Drug Tolerant Persisters [Parental (P) vs. Drug-Tolerant Persister (DTP)]

Project description:The Ontogeny and Vulnerabilities of Lapatinib Drug Tolerant Persisters [Parental (P) vs. Drug-Tolerant Persister (DTP)]

| PRJNA649434 | ENA

Single-cell transcriptomic analysis uncovers intratumoral heterogeneity and drug-tolerant persister in ALK-rearranged lung adenocarcinoma

Project description:Acquired drug resistance is the major therapeutic obstacle to maintenance treatment of advanced-stage non-small cell lung cancer. Lung adenocarcinoma (ADC) harboring driver mutations also showed poor response to immune checkpoint inhibitors (ICIs). Underlying mechanisms of how drug insensitivity evolves remain unclear. Here we explored the intratumoral heterogeneity of tyrosine kinase inhibitor (TKI)-resistant anaplastic lymphoma kinase (ALK)-rearranged lung ADC organoids using single-cell RNA-sequencing (scRNA-seq) transcriptomic analysis. IL-17 signaling pathway was found highly induced in a subpopulation of pre-existing ALK-TKI-resistant cells. These drug-tolerant persister (DTP) cells, also found to have high surface intracellular adhesion molecule 1 (ICAM-1) expression level, were more resistant towards ALK-TKI and expressed a higher level of cancer-stem cell transcriptional factors. Moreover, tumor cells with high ICAM-1 expression were found spatially correlated with RORɣt+ Th17 infiltration in ALK-rearranged NSCLC resected tumor tissues. In conclusion, our data revealed marked intratumoral heterogeneity in ALK-rearranged tumor, and pre-existing DTP cells may contribute to the development of drug insensitivity in ALK-rearranged lung ADC.

2023-08-09 | GSE223779 | GEO

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ATAC-seq]

Project description:Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. Whilst patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies. Here we profiled osimertinib DTPs using RNA-seq, ChIP-seq, and ATAC-seq to characterize the features of these cells and performed drug screens to identify therapeutic opportunities.

2022-04-06 | GSE193256 | GEO

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [RNA-seq]

2022-04-06 | GSE193258 | GEO

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [ChIP-seq]

2022-04-06 | GSE193257 | GEO

Drug tolerant persisters in erlotinib treated EGFR-mutated lung adenocarcinoma arise from pre-existing tumor cells and survive in an adapted stromal microenvironment [RNA-seq]

Project description:Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is thought to mainly be driven by minor subpopulations of drug tolerant persister (DTP) cells that survive the cytotoxic drug effect. In lung cancer, DTP studies have mainly been conducted using tumor cell line models.

2022-12-21 | GSE199716 | GEO

The Yin and Yang of GDF15: a secreted biomarker of eribulin response in breast cancer cells, yet required for survival of drug tolerant persister (DTP) cells

Project description:Drug tolerant persister (DTP) cells enter into a reversible slow-cycling state after cancer drug treatment. These cells are the living proof of response to a drug, and an interesting experimental subject for biomarker discovery. Here, we performed proteomic characterization of the breast cancer (BC) DTP cell secretome after eribulin treatment. First, we showed that eribulin induces a specific secretome in DTP cells as compared to other microtubule targeting agents. Then, we selected and functionally validated growth differentiation factor 15 (GDF15) as a protein significantly over-secreted upon eribulin treatment. Interestingly, GDF15 expression is low/absent in cells that are sensitive to eribulin, strongly upregulated during the response to the drug, and downregulated when stable resistance is ultimately established. Proteomic results were confirmed in 3D-cell culture models using BC cells lines and PDXs, as well as in a TNBC in vivo model. Unexpectedly, despite its biomarker potential for eribulin response, we found that GDF15 is also paradoxically required for survival of DTP cells, although once full resistance to eribulin is established, GDF15 expression largely disappears. Direct participation of GDF15 and its receptor GFRAL in eribulin-induction of DTPs was established by the enhanced cell killing of DTPs by eribulin seen under GDF15 and GFRAL loss of function conditions. These results pointed to a potential benefit of simultaneous targeting of GDF15/GFRAL and eribulin, and indeed we showed that combination therapy of eribulin plus an anti-GDF15 antibody kills BC-DTP cells. Our results suggest that targeting GDF15 may help eradicate DTP cells and block the onset of acquired eribulin resistance, and possibly other cytotoxic drugs. Overall, the combination of cytotoxic agents with targeted agents aimed specifically at DTP cells could be an effective therapeutic approach for metastatic breast cancer patients.

2023-01-09 | PXD034037 | Pride

Gene expression profiling of drug-tolerant persister BT474 breast cancer cells derived from lapatinib treatment

Project description:Acquired drug resistance prevents targeted cancer therapy from achieving stable and complete responses. Emerging evidence implicates a key role for nonmutational mechanisms including changes in cell state during early stages of acquired drug resistance. Targeting nonmutational resistance may therefore present a therapeutic opportunity to eliminate residual surviving tumor cells and impede relapse. A variety of cancer cell lines harbor quiescent, reversibly drug-tolerant âpersisterâ cells which survive cytotoxic drugs including targeted therapies and chemotherapies. These persister cells survive drug through nonmutational mechanisms which are poorly understood. Specifically targeting persister cells is a promising strategy to prevent tumor relapse. We sought to identify therapeutically exploitable vulnerabilities in persister cells using the HER2-amplified breast cancer line BT474 as an experimental model. Similar to other persister cell models, upon treatment with the HER2 inhibitor lapatinib (2uM concentration) for nine or more days, the majority of BT474 cells die, revealing a small population of quiescent surviving persister cells. Removal of lapatinib allows the persister cells to regrow and to re-acquire sensitivity to lapatinib. Subsequent lapatinib treatment re-derives persister cells. The reversibility of persister cell drug resistance indicates a nonmutational resistance mechanism. Here we provide RNAseq gene expression profiling data generated from parental BT474 cells compared to BT474 persister cells generated from nine days of treatment with 2 uM lapatinib. These data can be used to identify genes and pathways which are upregulated in persister cells, revealing potential therapeutic targets. 3 biological replicates of BT474 persister cells, two biological replicates of BT474 parental cells

2016-07-28 | E-GEOD-84896 | biostudies-arrayexpress

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