Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Evaluation of cetuximab-induced gene expression changes in residual PDX tumors of head and neck squamous cell carcinoma

ABSTRACT: Cetuximab, a monoclonal antibody targeting EGFR, offers only modest and often transient clinical responses in recurrent or metastatic HNSCC, owing to the persistence of a therapy-tolerant cell population that seeds residual disease and eventual therapeutic failure. Clinical evidence across cancer types indicates that depth of response to targeted therapy correlates with prolonged progression-free survival, highlighting the importance of residual disease as a driver of resistance. However, the molecular features enabling HNSCC cells to tolerate EGFR blockade before the acquisition of stable resistance remain incompletely understood. We analyzed residual tumors from cetuximab-treated patient-derived xenograft (PDX) models of HNSCC (#UCLHN04 and #HNC004) to identify gene expression changes associated with anti-EGFR tolerance in HNSCC cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE303798 | GEO | 2026/06/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Analysis of cetuximab-induced gene expression changes in head and neck squamous cell carcinoma cell lines

Project description:Despite recent advances in immunotherapy and anti-epidermal growth factor receptor (EGFR) treatments, the therapeutic landscape for locally advanced HNSCC has changed little over recent decades, and clinical outcome remains poor. Cetuximab, monoclonal antibody targeting EGFR, offers only modest and often transient clinical responses, owing to the persistence of a therapy-tolerant cell population that seeds residual disease and eventual therapeutic failure. Clinical evidence across cancer types indicates that depth of response to targeted therapy correlates with prolonged progression-free survival, highlighting the importance of residual disease as a driver of resistance. However, the molecular features enabling HNSCC cells to tolerate EGFR blockade before the acquisition of stable resistance remain incompletely understood. To uncover early transcriptional adaptations to EGFR inhibition, we performed bulk RNA-sequencing on FaDu and HN5 HNSCC cells treated with cetuximab for 72 hours.

2026-06-22 | GSE306480 | GEO

Unraveling cetuximab response in head and neck cancer with APHRODYTHE, a multi-omics patient-derived xenograft platform

Project description:The anti-EGFR antibody cetuximab is an established therapy for head and neck squamous cell carcinoma (HNSCC), yet robust predictive biomarkers of response remain elusive. To address this gap, we established APHRODYTHE, a resource of 79 HPV-negative HNSCC patient-derived xenografts (PDXs), including 61 with genomic annotation, 52 with RNA-seq profiling, and 63 tested with cetuximab in a population-scale preclinical trial. APHRODYTHE faithfully recapitulated the mutational, copy number, and transcriptional landscapes of human HNSCC, enabling systematic discovery of response determinants. Integrated multi-omics analyses revealed that tumors with pronounced squamous differentiation and keratinization were more likely to respond, whereas high Sonic Hedgehog (SHH) pathway activity was associated with intrinsic resistance. Cetuximab-sensitive tumors were also enriched for EGFR amplification, elevated EGFR ligand expression, and mutations in NOTCH1, FAT1, and ATM. Immunohistochemistry validated keratinization markers as candidate predictors of benefit with potential clinical applicability. Functionally, SHH pathway activation conferred antibody resistance, while pharmacologic SHH inhibition restored cetuximab sensitivity in resistant models. Together, these findings position APHRODYTHE as a robust translational platform, identify squamous keratinization and SHH activity as complementary biomarkers for patient stratification, and motivate SHH inhibition as a rational combination strategy to enhance cetuximab efficacy in HNSCC.

2026-01-30 | GSE317901 | GEO

Evaluation of gene expression changes upon acquired resistance to anti-EGFR targeted therapy in head and neck squamous cell carcinoma

Project description:We studied molecular mechanisms associated with acquired resistance to anti-EGFR targeted therapy in head and neck squamous cell carcinoma (HNSCC) by comparing gene expression profiles in cetuximab-sensitive and -resistant patient-derived xenograft (PDX) models of HNSCC. We generated and validated several HNSCC PDX models. Resistance mechanisms to anti-EGFR therapy were investigated in one of these PDX models (HNC004). First, sensitivity to cetuximab treatment was tested. This model showed high sensitivity to this drug. We induced acquired resistance to anti-EGFR therapy in this sensitive model by treating it chronically with anti-EGFR monoclonal antibody (cetuximab, 30 mg/kg/week) until resistance ensues. RNA-seq analysis was performed on samples coming from untreated and cetuximab-resistant PDX, revealing major changes of expression at the mRNA level.

2026-06-22 | GSE307896 | GEO

Evaluation of gene expression changes upon acquired resistance to anti-EGFR treatment in head and neck squamous cell carcinoma

Project description:We deciphered molecular mechanisms associated with acquired resistance to anti-EGFR targeted therapy in head and neck squamous cell carcinoma (HNSCC) by comparing gene expression profiles in cetuximab-sensitive and -resistant patient-derived xenograft (PDX) models of HNSCC. We generated and validated several HNSCC PDX models. Resistance mechanisms to anti-EGFR therapy were investigated in one of these PDX models (UCLHN04). First, sensitivity to cetuximab treatment was tested. This model showed high sensitivity to this drug. We induced acquired resistance to anti-EGFR therapy in this sensitive model by treating it chronically with anti-EGFR monoclonal antibody (cetuximab, 30 mg/kg/week) until resistance ensues. RNA-seq analysis was performed on samples coming from untreated and cetuximab-resistant PDX, revealing major changes of expression at the mRNA level.

2024-11-08 | GSE235417 | GEO

Genomic characterization of intrinsic and acquired resistance to cetuximab in colorectal cancer patients

Project description:Anti-EGFR antibodies are effective in therapies for late-stage colorectal cancer (CRC); however, many tumours are unresponsive or develop resistance. We performed genomic analysis of intrinsic and acquired resistance to anti-EGFR therapy in prospectively collected tumour samples from 25 CRC patients receiving cetuximab (an EGFR inhibitor). Of 25 CRC patients, 13 displayed intrinsic resistance to cetuximab; 12 were intrinsically sensitive. We obtained six re-biopsy samples at acquired resistance from the intrinsically sensitive patients. NCOA4–RET and LMNA–NTRK1 fusions and NRG1 and GNAS amplifications were found in intrinsic-resistant patients. In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. The comparison between baseline and acquired-resistant tumours revealed an extreme shift in variant allele frequency of somatic variants, suggesting that cetuximab exposure dramatically selected for rare resistant subclones that were initially undetectable. There was also an increase in epithelial-to-mesenchymal transition at acquired resistance, with a reduction in the immune infiltrate. Furthermore, characterization of an acquired-resistant, patient-derived cell line showed that PI3K/mTOR inhibition could rescue cetuximab resistance. Thus, we uncovered novel genomic alterations that elucidate the mechanisms of sensitivity and resistance to anti-EGFR therapy in metastatic CRC patients.

2019-09-21 | E-MTAB-8340 | biostudies-arrayexpress

Gene Expression profile of Cetuximab response in Colorectal Cancer Derived Xenograft

Project description:EGFR blockade by the monoclonal antibodies cetuximab or panitumumab causes objective tumor regressions in selected patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs almost invariably remain even after maximal response to therapy, leading to treatment failure and tumor relapse. Using mCRC patient-derived xenografts (PDXs), we observed that residual cancer cells surviving EGFR inhibition exhibited gene expression patterns reminiscent of a quiescent subpopulation of normal intestinal secretory precursors with Paneth-cell traits. These drug-tolerant cells had reduced expression of EGFR-activating ligands, consistent with lower EGFR dependence, and displayed higher HER2/HER3 pathway activity and persistent PI3K signaling. Mechanistically, cell fate reprogramming towards the Paneth cell-like phenotype was mediated by inactivation of YAP – a master regulator of intestinal epithelium recovery after injury – following cetuximab-induced neutralization of the MAPK cascade. Clinically, tumors from patients in whom cetuximab was not effective were enriched for markers of secretory commitment/Paneth-cell differentiation. In PDX therapeutic experiments, Pan-HER antibodies minimized residual disease burden and induced long-term tumor control after treatment discontinuation. We propose that tolerance to EGFR inhibition in CRC is typified by the adaptive disengagement of an in-built lineage program that jointly drives intestinal regenerative signaling and tumorigenesis. Further, our findings motivate therapeutic strategies to pre-emptively target residual disease before acquisition of irreversible resistance.

2020-05-06 | GSE108277 | GEO

Integrated single cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC sensitive cell lines

Project description:The identification of the potential mechanisms of resistance while tumor cells still respond to therapy is critical to develop combination therapies to delay acquired resistance. Cetuximab, an anti-EGFR therapy, is the only targeted therapy available for head and neck squamous cell carcinoma (HNSCC). We generated the first comprehensive multi-omics, bulk and single cell data in sensitive HNSCC cells to identify relevant transcriptional and epigenetic changes that are an immediate response to cetuximab in sensitive cells. These changes include genes from two pathways potentially associated with resistance: regulation of growth factor receptors through the transcription factor TFAP2A, and epithelial-to-mesenchymal transition (EMT) process. Single cell RNA-sequencing demonstrates inter-cell lines heterogeneity, with cell specific expression profiles of TFAP2A and VIM gene expression in cetuximab treated and untreated clones, and an independent role of each pathway. RNA-seq and ATAC-seq demonstrate that there are global transcriptional and epigenetic changes within the first five days of anti-EGFR therapy. We also experimentally verified that lack of TFAP2A reduces HNSCC growth in vitro and that this effect is enhanced with cetuximab and a stronger effect is observed with JQ1, an inhibitor of alternative receptor tyrosine kinases. Corroborating our scRNA-seq observation, TFAP2A silencing does not affect cell migration, supporting the lack of interplay with the EMT pathway. Overall, our study shows that the immediate adaptive transcriptional and epigenetic changes induced by cetuximab include relevant pathways associated with acquired resistance. Although heterogeneous, these changes can be targeted by a multiple-target drug as JQ1 that in combination with cetuximab in the early stage of treatment present better efficacy in controlling tumor growth.

2020-05-04 | GSE135604 | GEO

The expression profile of Cetuximab resistance in head-and-neck squamous cell carcinoma cells.

Project description:Cetuximab (Erbitux) is an antibody drug against EGFR and commonly used in late stage HNSCC and metastatic colorectal cancer. The oncogenic mutation of certain genes are known to drive Cetuximab resistance such as K-RAS or b-RAF mutation. The aberrant activation of signaling pathways in the presence of Cetuximab treatment to overcome cellular stress contribute to acquired resistance to Cetuximab as well. To better understand the mechanisms and molecular patterns of Cetuximab resistant cells, the Cetuximab resistant cells are trained for examining the gene expression profile. The gene expression array is used for identify the molecular signature governing the Cetuximab resitance.

2017-03-02 | GSE63916 | GEO

Integrated single cell and bulk gene expression and ATAC-seq reveals heterogeneity and early changes in pathways associated with resistance to cetuximab in HNSCC sensitive cell lines (scRNA-Seq)

2020-05-04 | GSE137524 | GEO

Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins

Project description:Unraveling the underlying mechanisms of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC) is of major importance as many tumors remain non-responsive or become resistant. Out microarray results suggest that resistant cells still exhibit RAS-MAPK pathway signaling contributing to drug resistance, as witnessed by low expression of DUSP 5 and DUSP6, negative regulators of ERK1/2, and increased expression of AURKB, a key regulator of mitosis. Therefore, interrupting the RAS-MAPK pathway by an ERK1/2 inhibitor (apigenin) or an AURKB inhibitor (barasertib) might be a new strategy for overcoming cetuximab resistance in HNSCC 4 head and neck squamous cell carcinoma (HNSCC) cell lines were treated with either 15 nM cetuximab or PBS during 13 hours. For each cell line, differential gene expression was assessed between cetuximab and PBS treatments.

2014-09-18 | E-GEOD-61495 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data