Intermittent treatment on exemestane acquired resistance
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA628626 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MCF7aro cells were cultured in hormone-stripped medium and treated with EXE continuously or intermittently (2 weeks on and 1 week off) in the presence of 1nM testosterone. At week 14, EXE-treated cells as well as MCF7aro cells were hormone-stripped for 48h were harvested and RNA was extracted.Gene expression profiles in each cell line were analyzed by the Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays.
2020-12-31 | GSE149406 | GEO
Project description:Melanoma patients receiving drugs targeting BRAFV600E and MKK1/2 invariably develop resistance and continue progression, limiting the efficacy of treatment. As an alternative to continuous dosing schedules, intermittent treatment strategies involving intervening periods of drug withdrawal have been proposed to delay resistance. The efficacy of this treatment strategy has been supported by preclinical findings and several clinical case reports. The beneficial effect of intermittent treatment has been attributed to “drug addiction”, in which the cell viability of resistant cells is compromised during periods of drug removal, presumably due to MAPK pathway hyperactivation. However, the cellular and molecular responses to intermittent treatment are still incompletely understood. Here, we investigate effects of intermittent treatment with the BRAFV600E inhibitor, encorafenib, in a metastatic melanoma cell line engineered to express genes conferring resistance to BRAF inhibition. We show that intermittent treatment shows superior growth suppression compared to continuous treatment for resistant cells that substantially reactivate the MAPK pathway. While drug addiction is clearly observable in these cells, it fails to account for the advantageous effects of intermittent treatment. Instead, growth suppression can mainly be explained by resensitization as most cell death is observed upon readdition of drug following periods of drug removal. Gene expression analysis shows that a unique and reversible transcriptional state is induced in intermittently treated cells following periods of drug removal. Thus, we conclude that the beneficial effects of intermittent treatment in our model are best explained by adaptive, non-mutational changes in transcription which confer drug resensitization.
2018-12-01 | GSE117123 | GEO
Project description:Acquired immunotherapy resistance in PDA
| PRJNA918626 | ENA
Project description:These studies are aimed at understanding gene expression chnages in a Her2 positive breast cancer cell line that has developed acquired resistance to lapatinib. Samples include SKBR3 parental and resistant (SKBR3-R) under basal conditions and in response to 0.1 and 1uM lapatinib treatment after 24 hours.
2012-06-30 | GSE38376 | GEO
Project description:Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance informs therapeutic strategies to effectively reprogram and reverse acquired resistance.
2024-01-11 | GSE249001 | GEO
Project description:Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance informs therapeutic strategies to effectively reprogram and reverse acquired resistance.
2024-01-11 | GSE249000 | GEO
Project description:Drug resistance is the principal challenge of cancer therapies, including recently developed immunotherapy. More and more popular use of immunotherapy, especially treatments with immune checkpoint inhibitors (ICIs), witnesses explosively increasing cases of both primary and acquired immunotherapy resistance. While primary resistance has been extensively studied, mechanisms underlying acquired resistance of immunotherapy are less understood. Here we reported that tumor cells could develop acquired resistance to ICI treatment through self-built collagen-containing physical barriers in non-small cell lung cancer (NSCLC). We found that tumor cells expressed high levels of multiple collagen genes, including COL3A1 and COL6A1, and were fully covered with collagen fibers. COL3A1 formed a castle-like structure of a cluster of tumor cells and prevented the infiltration of T cells, while COL6A1 seemed to be an armor-like structure of each tumor cell and protected them from attack by cytotoxic T cells. Genetic or pharmaceutic disruption of these collagens, by warfarin, a commonly used medicine, significantly reversed the acquired resistance. Thus, our data reveal an unprecedented tumor cell-intrinsic mechanism, mediated by collagen-containing physical barriers, of acquired immunotherapy resistance, which immediately suggests a treatment option for patients.
2025-02-01 | GSE261898 | GEO
Project description:Drug resistance is the principal challenge of cancer therapies, including recently developed immunotherapy. More and more popular use of immunotherapy, especially treatments with immune checkpoint inhibitors (ICIs), witnesses explosively increasing cases of both primary and acquired immunotherapy resistance. While primary resistance has been extensively studied, mechanisms underlying acquired resistance of immunotherapy are less understood. Here we reported that tumor cells could develop acquired resistance to ICI treatment through self-built collagen-containing physical barriers in non-small cell lung cancer (NSCLC). We found that tumor cells expressed high levels of multiple collagen genes, including COL3A1 and COL6A1, and were fully covered with collagen fibers. COL3A1 formed a castle-like structure of a cluster of tumor cells and prevented the infiltration of T cells, while COL6A1 seemed to be an armor-like structure of each tumor cell and protected them from attack by cytotoxic T cells. Genetic or pharmaceutic disruption of these collagens, by warfarin, a commonly used medicine, significantly reversed the acquired resistance. Thus, our data reveal an unprecedented tumor cell-intrinsic mechanism, mediated by collagen-containing physical barriers, of acquired immunotherapy resistance, which immediately suggests a treatment option for patients.
2025-02-01 | GSE261890 | GEO
Project description:Intermittent Drug Treatment of BRAFV600E Melanoma Cells Delays Resistance by Sensitizing Cells to Rechallenge
| PRJNA481166 | ENA
Project description:This study was conducted to identify dysregulated genes associated with acquired resistance to chemotherapy. Endoscopic biopsy samples were collected from CF-treated metastatic gastric cancer patients prior to therapy and following the development of resistance to therapy.
2011-06-01 | E-GEOD-14209 | biostudies-arrayexpress