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Breast cancer cell lines treated with eribulin and paclitaxel

ABSTRACT: Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE50811 | GEO | 2014/10/02

SECONDARY ACCESSION(S): PRJNA219068

REPOSITORIES: GEO

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Breast cancer cell lines treated with eribulin and paclitaxel

Project description:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. 27 breast cancer cell lines treated with eribulin and paclitaxel for 24 hours at concentration 10xIC50. Three technical replicates were included. for eribulin , paclitaxel and untreated cell lines.

2014-10-02 | E-GEOD-50811 | biostudies-arrayexpress

Endometrial cancer cell lines treated with eribulin and paclitaxel

Project description:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. 19 endometrial cancer cell lines treated with eribulin and paclitaxel for 24 hours at concentration 10xIC50. Three technical replicates were included. for eribulin , paclitaxel and untreated cell lines.

2014-10-02 | E-GEOD-50830 | biostudies-arrayexpress

Ovarian cancer cell lines treated with eribulin and paclitaxel

Project description:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. 21 ovarian cancer cell lines treated with eribulin and paclitaxel for 24 hours at concentration 10xIC50. Three technical replicates were included for eribulin , paclitaxel and untreated cell lines.

2014-10-02 | E-GEOD-50831 | biostudies-arrayexpress

Ovarian cancer cell lines treated with eribulin and paclitaxel

2014-10-02 | GSE50831 | GEO

Endometrial cancer cell lines treated with eribulin and paclitaxel

2014-10-02 | GSE50830 | 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

MiRNA biomarkers for eribulin response

Project description:Background: Recent phase II and III clinical trials demonstrated antitumor activity of eribulin, a tubulin-interacting cytotoxic agent, in patients with metastatic soft tissue sarcoma (STS). In this exploratory study we aimed to identify putative microRNA biomarkers that associate with eribulin sensitivity or resistance in STS. Materials and methods: Archival tumor tissue from primary tumors or metastatic lesions was collected prior to eribulin treatment, from 65 consenting patients involved in the EORTC trial 62052. This phase II study (ClinicalTrials.gov identifier NCT00413192) included multiple subtypes of STS. Tissue was available from 21 leiomyosarcomas, 14 adipocytic sarcomas, 9 synovial sarcomas and 21 other sarcoma histotypes. Total RNA was isolated from formalin fixed, paraffin embedded tumor samples and analyzed using Taqman® Low Density Arrays to determine microRNA expression profiles. The expression of a total of 756 microRNAs was assessed. Progression free survival at week 12 (RECIST 1.0) measured as a binary variable, was the primary endpoint of the clinical trial and used as a primary response measure for correlative studies. Seventeen out of 53 (32.1%) evaluable patients in the analyzed subset had non-progressive disease at week 12 and were defined as responders. Results: The expression of 26 individual microRNAs (p<0.05) differed significantly between non-responders and responders. Additional microRNAs of potential relevance were identified when considering the different histological subgroups. Conclusions: The expression level of particular microRNAs in STS tissue samples may predict response to eribulin. Further validation studies as well as a preclinical assessment of the underlying molecular mechanisms are required.

2017-02-20 | GSE87902 | GEO

Alteration of DNMT1/DNMT3A by eribulin elicits global DNA methylation changes with potential therapeutic implications for triple-negative breast cancer

Project description:Triple-negative breast cancer (TNBC) is an aggressive disease subtype with limited treatment options. Eribulin is a chemotherapeutic approved for the treatment of advanced breast cancer that has been shown to elicit epigenetic changes. We investigated the effect of eribulin treatment on genome-scale DNA methylation patterns in TNBC cells. Following repeated treatment, The results showed that eribulin-induced changes in DNA methylation patterns evident in persister cells. Eribulin also affected the binding of transcription factors to genomic ZEB1 binding sites and regulated several cellular pathways, including ERBB and VEGF signaling and cell adhesion. Eribulin also altered the expression of epigenetic modifiers including DNMT1, TET1, and DNMT3A/B in persister cells. Data from primary human TNBC tumors supported these findings: DNMT1 and DNMT3A levels were altered by eribulin treatment in human primary TNBC tumors. Our results suggest that eribulin modulates DNA methylation patterns in TNBC cells by altering the expression of epigenetic modifiers. These findings have clinical implications for using eribulin as a therapeutic agent.

2023-12-31 | GSE234881 | GEO

Eribulin is an immune potentiator in breast cancer by up-regulating human leukocyte antigen class I expression via the induction of NLRC5

Project description:The effect of Eribulin in RNA expression was addressed by RNA-sequence using Eribulin treated MCF7 breast cancer cell line.

2023-12-27 | GSE226836 | GEO

Evaluation of Eribulin Combined with Irinotecan for Treatment of Pediatric Cancer Xenografts

Project description:Eribulin, irinotecan, and the combination were studied in ES4 xenograft model. RNAs from xenograft tumors were harvested at 24h and 144h after single agent or combination treatment to analyze gene expression.

2020-03-10 | GSE146687 | GEO

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