Genetic, clinical, and biomarker correlates of EGFR inhibitor-related rash
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE115468 | GEO | 2021/06/07
REPOSITORIES: GEO
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Project description:Genetic, clinical, and biomarker correlates of EGFR inhibitor-related rash
| PRJNA475113 | ENA
Project description:Non-small cell lung cancers (NSCLCs) harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as erlotinib and geffitinib. However, nearly all patients show relapse within 1 year after initial treatment. We used microarrays to detail global gene expression changes in EGFR mutant cells vs. WT cells responding to erlotinib. 4 EGFR mutant and 4 WT NSCLC cells were treated with or without erlotinib for 24 hr, followed by RNA extraction and hybridization on Affymetrix microarrays.
2014-05-16 | E-GEOD-57156 | biostudies-arrayexpress
Project description:Non-small cell lung cancers (NSCLCs) harboring activating EGFR mutants show dramatic responses to EGFR TKIs, such as erlotinib and geffitinib. However, nearly all patients show relapse within 1 year after initial treatment. We used microarrays to detail global gene expression changes in EGFR mutant cells vs. WT cells responding to erlotinib.
2014-05-16 | GSE57156 | GEO
Project description:Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
2024-11-10 | GSE281529 | GEO
Project description:The goal of this study was to compare the transcriptome (RNA-seq) of EGFR TKI sensitive NSCLC cells with that of cells with acquired resistance to erlotinib. HCC827 and HCC4006 cells were continuously cultured in erlotinib until erlotinib resistant (ER) variants emerged. All ER variants were negative for T790M. RNA from parental and ER cells was isolated for transcriptomic profiling. RNA-seq analysis reveals that EGFR TKI resistance is associated with a mesenchymal gene expression signature.
2020-09-03 | GSE121634 | GEO
Project description:Analysis of human, adult, dermal fibroblasts following treatment with 100nM or 1 uM of erlotinib, a tryrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR) inhibiting EGFR activation and signaling. Erlotinib is widely used to effectively treat patients with advanced non-small cell lung cancer but treatment with erlotinib and other EGFR TKIs are associated with a painful skin rash. Results identified significantly differentially expressed genes in fibroblasts treated with erlotinib providing insight into how the drug alters the transcriptome in ways that may contribute to the TKI-related rash.
2019-01-01 | GSE106151 | GEO
Project description:Aim: The goals of this study were to identify transcriptomic changes that arise in basal-like breast cancer cells during the development of resistance to epidermal growth factor receptor inhibitors (EGFRi) and to identify drugs that are cytotoxic once EGFRi resistance occurs. Methods: Human patient-derived xenografts (PDXs) were grown in immunodeficient mice and were treated with a set of EGFRi; the EGFRi erlotinib was selected for more expansive in vivo studies. Single-cell RNA sequencing was performed on mammary tumors from the basal-like PDX WHIM2 that was treated with vehicle or erlotinib for nine weeks. The PDX was then subjected to long-term erlotinib treatment in vivo and through serialserially passaging, an erlotinib-resistant subline of WHIM2 was generated. Bulk RNA-sequencing was performed on parental and erlotinib-resistant tumors. In vitro high-throughput drug screening with >500 clinically used compounds was performed on parental and erlotinib-resistant cells. Previously published bulk gene expression microarray data from MMTV-Wnt1 tumors were contrasted with the WHIM2 PDX data. Results: Erlotinib effectively inhibited WHIM2 tumor growth for ~four weeks. Compared to untreated cells, single-cell RNA sequencing revealed that a greater proportion of erlotinib-treated cells were in the G1 phase of the cell cycle. Comparison of WHIM2 and MMTV-Wnt1 RNA level data revealed a set of 37 overlapping genes that were differentially expressed in the erlotinib-resistant subsets of WHIM2 and MMTV-Wnt1 tumors. Comparison of all three data types revealed five genes that were upregulated across all erlotinib-resistant samples: IL19, KLK7, LCN2, SAA1, and SAA2. Despite transcriptomic differences, parental and erlotinib-resistant WHIM2 displayed similar responses to the majority of drugs assessed for cytotoxicity in vitro. Conclusion: This study identified transcriptomic changes arising in erlotinib-resistant basal-like breast cancer. Interestingly, four of the five genes that were found to be upregulated in the basal-like erlotinib-resistant samples were also upregulated in erlotinib-resistant non-small cell lung cancer samples. These gene signatures could be used to identify basal-like breast cancer patients that would best respond to EGFRi. Future studies should explore the predictive capacity of these gene signatures as well as how these differentially expressed genes contribute to the development of EGFRi resistance.
2022-12-07 | GSE189324 | GEO
Project description:Aim: The goals of this study were to identify transcriptomic changes that arise in basal-like breast cancer cells during the development of resistance to epidermal growth factor receptor inhibitors (EGFRi) and to identify drugs that are cytotoxic once EGFRi resistance occurs. Methods: Human patient-derived xenografts (PDXs) were grown in immunodeficient mice and were treated with a set of EGFRi; the EGFRi erlotinib was selected for more expansive in vivo studies. Single-cell RNA sequencing was performed on mammary tumors from the basal-like PDX WHIM2 that was treated with vehicle or erlotinib for nine weeks. The PDX was then subjected to long-term erlotinib treatment in vivo and through serialserially passaging, an erlotinib-resistant subline of WHIM2 was generated. Bulk RNA-sequencing was performed on parental and erlotinib-resistant tumors. In vitro high-throughput drug screening with >500 clinically used compounds was performed on parental and erlotinib-resistant cells. Previously published bulk gene expression microarray data from MMTV-Wnt1 tumors were contrasted with the WHIM2 PDX data. Results: Erlotinib effectively inhibited WHIM2 tumor growth for ~four weeks. Compared to untreated cells, single-cell RNA sequencing revealed that a greater proportion of erlotinib-treated cells were in the G1 phase of the cell cycle. Comparison of WHIM2 and MMTV-Wnt1 RNA level data revealed a set of 37 overlapping genes that were differentially expressed in the erlotinib-resistant subsets of WHIM2 and MMTV-Wnt1 tumors. Comparison of all three data types revealed five genes that were upregulated across all erlotinib-resistant samples: IL19, KLK7, LCN2, SAA1, and SAA2. Despite transcriptomic differences, parental and erlotinib-resistant WHIM2 displayed similar responses to the majority of drugs assessed for cytotoxicity in vitro. Conclusion: This study identified transcriptomic changes arising in erlotinib-resistant basal-like breast cancer. Interestingly, four of the five genes that were found to be upregulated in the basal-like erlotinib-resistant samples were also upregulated in erlotinib-resistant non-small cell lung cancer samples. These gene signatures could be used to identify basal-like breast cancer patients that would best respond to EGFRi. Future studies should explore the predictive capacity of these gene signatures as well as how these differentially expressed genes contribute to the development of EGFRi resistance.
2022-12-07 | GSE189257 | GEO
Project description:Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
2024-11-08 | GSE281096 | GEO
Project description:Activating mutations of EGFR have been characterized as important mechanisms for carcinogenesis in a subset of EGFR-dependent non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib, have dramatic clinical effects on EGFR-addicted lung cancers and are used as first-line therapy for EGFR-mutant tumors. However, eventually all tumors acquire secondary resistance to the drugs and progress. We established a model to better understand mechanisms of acquired resistance. NCI- HCC827 cells are EGFR-mutant and highly erlotinib-sensitive. In this study we exposed HCC827 cells to increasing concentrations of erlotinib and two highly erlotinib-resistant subclones were developed (ER3 and T15-2). In these subclones no acquired alterations of EGFR or MET were found. We hereby performed a gene expression microarray studies to understand changes that might explain mechanisms of resistance. Through these studies we demonstrated in one resistant clone (ER3) overexpression of AXL, a tyrosine kinase implicated in imatinib and lapatinib resistance. Gene expression profilings were measured in NSCLC cell line HCC827 and two erlotinib-resistant HCC827-originated sublines ER3 and T15-2.
2012-05-29 | E-GEOD-38310 | biostudies-arrayexpress