Dataset Information

The changes in HNSCC cell lines (e.g., OECM1) when treated with Cetuximab (500 ug/ml) at different passages. We used LC-MS/MS to identify the main target pathway. These findings could significantly enhance our evidence.

ABSTRACT: Recent clinical trials revealed that prior use of Cetuximab may interfere with ICB efficacy. In this study, STAT1 protein levels changed after continued Cetuximab treatment (500 ug/ml). We collected serial passages of cetuximab resistance HNSCC cell lines to perform LC-MS/MS. We identified the IFN pathway as the key target to cause this effect.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Po-Hsien Chiu

LAB HEAD: Muh-Hwa Yang

PROVIDER: PXD054113 | Pride | 2025-12-29

REPOSITORIES: Pride

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			Action	DRS
	20231131-A0908-0p5ug-10.mzML	Mzml
	20231131-A0908-0p5ug-10.mzid.gz	Mzid
	20231131-A0908-0p5ug-10.raw	Raw
	20231131-A0908-0p5ug-6.mzML	Mzml
	20231131-A0908-0p5ug-6.mzid.gz	Mzid

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Publications

Therapeutic stress triggers tumor STAT1 acetylation to disarm immunotherapy.

Chiu Po-Hsien PH Lai Kuan-Chen KC Wang Hung-Ling HL Chang Yao-Wen YW Wu Wen-Chi WC Chen Tien-Hua TH Tsai Yu-Shuen YS Song Jie-Hong JH Sun Nai-Yun NY Chau Gar-Yang GY Fang Wen-Liang WL Chen Ju-Pei JP Wang Hung-Ming HM Huang Huai-Cheng HC Hsieh Meng-Che MC Hua Chun-Hung CH Lien Ming-Yu MY Chang Yi-Fang YF Wang Hui-Ching HC Chien Chih-Yen CY Huang Tai-Lin TL Wang Chen-Chi CC Liu Yi-Chun YC Chen Jo-Pai JP Lu Wei-Chen WC Yiu Ching-Yi CY Lin Chien-Liang CL Lou Pei-Jen PJ Chu Pen-Yuan PY Wang Shao-Chun SC Hung Mien-Chie MC Yang Muh-Hwa MH

Cell reports. Medicine 20251107 11

Sequential cancer therapy presents a critical challenge, as the impact of prior treatments on immunotherapy remains unclear. Here, we demonstrate that therapeutic stress from prolonged cetuximab exposure induces tumor-intrinsic resistance to immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma (HNSCC). In a multicenter analysis, extended cetuximab treatment correlates with poor ICB response and survival. Mechanistically, chronic therapeutic stress provokes an initial inflamm ...[more]

PMID: 41205596

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Project description:Abstract Background. Epidermal growth factor receptor (EGFR) is a targetable molecule in basal-like breast cancer, which comprises most “triple negative” breast cancer (TNBC), the only breast cancer subtype without established targeted therapy. Methods. In this randomized phase II trial, metastatic TNBC patients received the anti-EGFR antibody cetuximab (250mg/kg/week iv) with carboplatin (AUC2/wk iv) added on progression, or concomitant cetuximab + carboplatin. Molecular subtyping was done on archival specimens and those with accessible tumors provided fresh tissue, before and after 7-14 days of therapy, for microarray analyses to explore EGFR pathway inhibition. Results. Of 102 TNBC patients 74% were of the basal-like molecular subtype. Response rate to cetuximab was 6% (2/31), and was 16% (4/25) to cetuximab + carboplatin after progression. Upfront cetuximab + carboplatin produced responses in 17% (12/71); 31% responded or had prolonged disease stabilization. Time to progression was 2.1 months (95% CI 1.8-5.5) and overall survival 10.4 months (95% CI 7.7-13.1) for those treated with the combination regimen. Among 16 patients with evaluable serial biopsies, genomic patterns of the EGFR pathway showed activated status in 13 and inhibition by therapy in 5. Conclusions. While most TNBC were basal-like, a significant proportion were different subtypes. The aggressive nature of metastatic TNBC leads to limited survival. Despite a promising preclinical rationale and evidence of EGFR pathway activation in most, targeted treatment with cetuximab as a single agent had marginal activity and cetuximab added to carboplatin demonstrated modest activity. Serial biopsies as part of metastatic breast cancer studies are feasible, and this study confirmed that the EGFR pathway was inhibited by therapy in only a minority suggesting ligand-independent activation in most tumors. Tissue acquisition and drug selection based upon individualized pathway activation status should be an important part of future studies of TNBC. This series contains 36 microarrays that are from 18 patients with fresh frozen tissue available from the metastatic site. Pretreatment samples (Bx0) are available for two patients. Pretreatment and post single agent treatment (7-14 days after start of treatment with cetuximab; BxSingle) are available for three patients. Pretreatment and post combination treatment (7-14 days after start of treatment with cetuximab plus carboplatin; BxCombo) are available for eight patients. Two patients have a pretreatment sample, a sample after 7-14 days of treatment with single agent cetuximab, and a third sample 7-14 days on cetuximab plus carboplatin after switching to the combination arm upon progression on the single agent arm. Samples were hybridized with Stratagene common reference spiked with RNA from two breast cancer cell lines (ME16C and MCF-7) on Custom 1x44K Agilent microarrays. Arrays were scanned on an Axon 4000B scanner and analyzed with GenePix Pro software.