Clinical significance of the expression of EGFR signaling pathway-related proteins in esophageal squamous cell carcinoma

Li, Jiancheng; Zhao, Yun-hui; Wang, Xiaoying; Yang, Yan; Pan, Dinglong; Qiu, Zidan; Su, Ying; Pan, Jianji

doi:10.1007/s13277-013-1089-0

Cited by 18 publications

(19 citation statements)

References 17 publications

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“…The frequent amplification of EGFR and closely related ERBB2 can contribute to elevated receptor activity in HNSCCs and ESCCs (Li et al, 2014). Interestingly, in a recent comprehensive study of HNSCCs, EGFR amplification was found in 15% of the (HPV-) tumors but in none of their (HPV+) counterparts (Cancer Genome Atlas, 2015).…”

Section: Tyrosine Kinase Receptorsmentioning

confidence: 99%

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

2016

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SUMMARY Squamous cell carcinomas (SCCs) represent the most frequent human solid tumors and a major cause of cancer mortality. These highly heterogeneous tumors arise from closely interconnected epithelial cell populations with intrinsic self-renewal potential inversely related to the stratified differentiation program. SCCs can also originate from simple or pseudo-stratified epithelia through activation of quiescent cells and/or a switch in cell fate determination. Here, we focus on specific determinants implicated in the development of SCCs by recent large-scale genomic, genetic and epigenetic studies and complementary functional analysis. This evidence indicates that SCCs from various body sites, while clinically treated as separate entities, have common determinants, pointing to a unified perspective of the disease and potential new avenues for prevention and treatment.

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Section: Tyrosine Kinase Receptorsmentioning

confidence: 99%

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

2016

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“…28,29 In addition, overexpression of the EGFR gene occurs across a wide range of different cancers, including brain, colorectal, lung, esophageal, cervical cancers, and sarcoma. [30][31][32][33][34][35] CDH1 and VEGFA have been reported among the highly significant markers in colorectal, gastric, and liver cancers. [36][37][38][39][40][41] The 154-gene expression signature shows clear promise in identifying the tumor's origin, but it is not perfect.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer transcriptome analysis reveals a gene expression signature for the identification of tumor tissue origin

Xu¹,

Chen²,

et al. 2016

Modern Pathology

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Carcinoma of unknown primary, wherein metastatic disease is present without an identifiable primary site, accounts for~3-5% of all cancer diagnoses. Despite the development of multiple diagnostic workups, the success rate of primary site identification remains low. Determining the origin of tumor tissue is, thus, an important clinical application of molecular diagnostics. Previous studies have paved the way for gene expression-based tumor type classification. In this study, we have established a comprehensive database integrating microarray-and sequencing-based gene expression profiles of 16 674 tumor samples covering 22 common human tumor types. From this pan-cancer transcriptome database, we identified a 154-gene expression signature that discriminated the origin of tumor tissue with an overall leave-one-out cross-validation accuracy of 96.5%. The 154-gene expression signature was first validated on an independent test set consisting of 9626 primary tumors, of which 97.1% of cases were correctly classified. Furthermore, we tested the signature on a spectrum of diagnostically challenging tumors. An overall accuracy of 92% was achieved on the 1248 tumor specimens that were poorly differentiated, undifferentiated or from metastatic tumors. Thus, we have identified a 154-gene expression signature that can accurately classify a broad spectrum of tumor types. This gene panel may hold a promise to be a useful additional tool for the determination of the tumor origin.

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“…Aberrant EGFR activity in tumors can arise through gene amplification, somatic mutation, overexpression of EGFR protein, or increased exposure to ligands . EGFR overexpression occurs in 32%‐86% of ESCCs …”

Section: Introductionmentioning

confidence: 99%

Phase I dose‐escalation trial of Sym004, an anti‐EGFR antibody mixture, in Japanese patients with advanced solid tumors

et al. 2018

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Sym004 is a 1:1 mixture of two antibodies targeting non‐overlapping epitopes of the epidermal growth factor receptor that antagonizes ligand binding and induces receptor downregulation. In preclinical models, it has superior antitumor activity to cetuximab and panitumumab. Japanese adults aged ≥20 years with an Eastern Cooperative Oncology Group status of 0/1 and life expectancy ≥3 months were eligible. Patients in Part A (dose escalation) had refractory or recurrent late‐stage solid tumors and received Sym004 6 mg/kg/wk (n = 3), 9 mg/kg loading/6 mg/kg/wk (n = 6), 12 mg/kg/wk (n = 6), or 18 mg/kg biweekly (n = 6). Patients in expansion Part B (n = 30) had esophageal squamous cell carcinoma and received Sym004 at the dose recommended from Part A. Fifty‐one patients received Sym004. No dose‐limiting toxicities were observed in Part A. A dose of 12 mg/kg/wk was selected for Part B. All patients in Part B experienced treatment‐related adverse events, most commonly dermatitis acneiform (76.7%). Eighteen grade ≥3 treatment‐related adverse events and five serious adverse events occurred (cardiac arrest, lung infection, interstitial lung disease, toxic skin eruption, blood creatinine increase). Two patients had treatment‐related adverse events resulting in death (cardiac arrest and blood creatinine increase). Five patients in Part B had a best overall response of partial response, 12 stable diseases and 12 disease progression (1 not evaluable). The objective response rate was 16.7% (95% CI: 5.6%‐34.7%). Sym004 therapy was well tolerated with no dose‐limiting toxicities at any dose studied. Evidence of antitumor activity was seen in patients with esophageal squamous cell carcinoma. ClinicalTrials.gov Identifier: NCT01955473.

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Clinical significance of the expression of EGFR signaling pathway-related proteins in esophageal squamous cell carcinoma

Cited by 18 publications

References 17 publications

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

Squamous Cell Cancers: A Unified Perspective on Biology and Genetics

Pan-cancer transcriptome analysis reveals a gene expression signature for the identification of tumor tissue origin

Phase I dose‐escalation trial of Sym004, an anti‐EGFR antibody mixture, in Japanese patients with advanced solid tumors

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