Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199716 | GEO | 2022/12/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

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

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. We conducted an in vivo DTP study using a lung adenocarcinoma (LUAD) patient-derived xenograft (PDX) tumor driven by an epidermal growth factor receptor (EGFR) mutation. Daily treatment of tumor-bearing mice for 5-6 weeks markedly shrunk the tumors and generated DTPs, which were analyzed by bulk population transcriptome.

2022-12-21 | GSE198672 | GEO

Drug-tolerant cancer cell persisters survive lethal exposures by silencing transposable elements [ChIP-Seq]

Project description:Establishing and maintaining phenotypic heterogeneity within cell and organismal populations is an evolutionarily conserved strategy that ensures survival of the population following stressful exposures. We previously identified a transient, reversible, drug-tolerant cancer cell subpopulation that survives otherwise lethal drug exposures. Here we show that these drug-tolerant persisters (DTPs) assume a highly heterochromatic state, which requires factors that modify or bind trimethylated H3 lysine 9 (H3K9me3). The increased H3K9me3 in DTPs is largely restricted to evolutionarily young Long Interspersed Repeat elements (LINEs). This transcriptionally repressive state, which decreases the expression of these retrotransposable elements, is critical for DTP survival, and disruption of this heterochromatic state results in re-expression of LINE elements and ablation of this subpopulation. Together, these findings establish a role for epigenetic silencing of transposable elements as a population survival strategy to maintain genomic integrity in subpopulations of cancer cells during lethal drug exposures.

2017-07-03 | GSE74179 | GEO

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

Project description:Drug tolerant persisters in erlotinib treated EGFR-mutated lung adenocarcinoma arise from pre-existing tumor cells and survive in an adapted stromal microenvironment

| PRJNA816436 | ENA

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: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]

| PRJNA821227 | ENA

The Ontogeny and Vulnerabilities of Lapatinib Drug Tolerant Persisters [NPY1R]

Project description:Despite significant advances in HER2-targeted therapies, therapeutic resistance in HER2-positive (HER2+) breast cancer remains a significant clinical problem, especially in the metastatic setting. “Drug tolerant persisters” (DTPs), a sub-population of cancer cells that survive via reversible, non-genetic mechanisms, are implicated in resistance to tyrosine kinase inhibitors (TKIs) in several cancer models, but DTPs for HER2-targeted TKIs (e.g., lapatinib, neratinib, tucatinib) have not been characterized extensively. Here, we report that HER2+ER+ and HER2+ER- breast cancer lines give rise to distinct types of “lapatinib-DTPs,” characterized by different transcriptional programs and sensitivity to lapatinib/anti-estradiol combination. Lapatinib-DTPs from HER2+/ER+ cells rewire the PI3K/AKT/mTORC1 pathway via transcriptional induction of SGK3 to enable AKT-independent mTORC1 activation and survival. Lentiviral barcoding experiments, combined with single cell RNA-sequencing, suggest that HER2+ cells stochastically cycle through a cell state (“pre-DTP”) capable of transition to DTPs. Collectively, our results provide insight into DTP ontogeny and therapeutic vulnerabilities.

2021-12-31 | GSE155227 | GEO

Cycling cancer persisters arise from lineages with distinct transcriptional and metabolic programs

Project description:Non-genetic mechanisms have recently emerged as important drivers of therapy failure in cancer, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment. While most cancer persisters, like their bacterial counterparts, remain arrested in the presence of drug, a rare subset of cancer persisters can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to simultaneously resist therapy and maintain proliferative capacity in the presence of drug. To address this, we developed Watermelon, a new high-complexity expressed barcode lentiviral library for simultaneous tracing each cell's clonal origin, proliferative state, and transcriptional state, and used it to study this rare, transiently-resistant, proliferative persister population and identify what distinguishes it from non-cycling persisters. Analysis of Watermelon-transduced cancer cell lines demonstrated that cycling and non-cycling persisters arise from different pre-existing cell lineages with distinct transcriptional and metabolic programs. The proliferative capacity of persisters is associated with an upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation in specific subpopulations of tumor cells.

2020-05-21 | GSE150949 | GEO

Colorectal cancer cells possess an equipotent capacity to enter a reversible diapause-like state to survive chemotherapy

Project description:Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from chemotherapies and targeted agents. It is increasingly appreciated that DTPs are an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target DTPs.

2021-01-07 | GSE145356 | GEO

C-ATF6 improves EGFR tyrosine kinase inhibitor sensitivity in non-small cell lung cancer via modulation of the calcium homeostasis network.

Project description:Osimertinib (Osi) is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and its clinical efficacy is limited due to the emergence of resistance. We found that parental cells undergo a drug-tolerant persister (DTP) state before ultimately achieving acquired resistance. In this study, we restored the specifically dysregulated circular RNA (cATF6) in the DTP state and used it in combination with Osimertinib, finding that it could significantly synergistically target DTP tumor cells. Mechanistically, it mainly disrupted the balance of Ca2+, ultimately leading to the death of DTP cells due to Ca2+ overload. This study reveals the impact of cATF6 on the dynamic balance of calcium ions, which may bring new strategies for epidermal growth factor receptor inhibitors (EGFR-TKIs) to eradicate DTP.

2025-01-02 | GSE285632 | GEO

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

2021-12-31 | GSE155341 | 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