Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI–Mediated Anticancer Activity in NSCLC

Zheng, Yang; Chan, Kin Iong; Kwok, Hang Fai; Tam, Kin Yip

doi:10.1016/j.tranon.2019.08.003

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…It is estimated that approximately 25% of cancer cases are related to infectious diseases and chronic inflammation (40). The reduction of inflammatory molecule production has been shown to enhance the sensitivity of NSCLC with EGFR mutation to EGFR-TKIs (41). In support of the hypothesis that inflammation is associated with cancer development and progression and also influence the response to treatment, we found that 3 SNPs (rs10519613, rs4819554, and rs4149570) and 5 SNPs (rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) were associated with worse PFS and OS of advanced NSCLC patients treated with EGFR-TKIs, respectively.…”

Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Zhang

et al. 2022

Front. Oncol.

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BackgroundInflammation is not only involved in the development and progression of cancer but also affects the response to therapy. The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) in inflammation genes with the prognosis of advanced non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).MethodsForty-seven SNPs were genotyped in 318 advanced NSCLC patients receiving EGFR-TKIs. Of 318 patients, 182 (57.2%) patients died during follow-up period. We assessed the association of SNPs with the progression-free survival (PFS) and overall survival (OS) as well as calculated the weighted genetic risk score (GRS). We also explored the expression levels and prognostic values of inflammation genes in lung adenocarcinoma (LUAD) in Gene Expression Profiling Interactive Analysis (GEPIA) and using UCSC Xena, respectively. The relationship between the expression levels of IL15, IL17RA, AGER, MIF, and TNFRSF1A and EGFR mutation status was analyzed using UCSC Xena.ResultsIn single variant analyses, 3 SNPs (rs10519613, rs4819554, and rs4149570) were significantly associated with worse PFS. Five SNPs (rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) were significantly with worse OS. In addition, high and intermediate GRSs (based on rs10519613, rs4819554, and rs4149570) were associated with worse PFS than those with low GRS. For OS, patients with high GRSs (based on rs10519613, rs4819554, rs2070600, rs755622, and rs4149570) had shorter survival time than those with low GRS. Furthermore, IL15, IL17RA, AGER, MIF, and TNFRSF1A were dysregulated in LUAD. There was difference in the expression level of TNFRSF1A between EGFR wildtype and EGFR-mutant LUAD. Both low AGER expression and high TNFRSF1A expression were significantly associated with worse PFS in LUAD. In addition, low IL17RA and AGER expression, high MIF and TNFRSF1A expression were significantly associated with worse OS in LUAD.ConclusionSNPs in inflammation genes could serve as prognostic biomarkers for NSCLC patients treated with EGFR-TKIs.

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Section: Discussionmentioning

confidence: 99%

Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Zhang

et al. 2022

Front. Oncol.

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“…In lung adenocarcinoma tissues, the number of phospho-ADAM17-positive cells was significantly increased in KRAS-mutated tumors than in the tumors with wild-type KRAS [89]. Additionally, ADAM17 is highly expressed in EGFR-mutated NSCLC cells, where an anti-ADAM17 antibody enhances EGFR-TKI-mediated growth inhibition, which is accompanied with reduced ERK phosphorylation [90]. Therefore, it is possible that such oncogenic drivers induce the EREG-mediated oncogenic activation of EGFR signaling through regulating ADAM17 activity in NSCLC.…”

Section: Ereg In Oncogene-driven Nsclcmentioning

confidence: 99%

Role of Epiregulin in Lung Tumorigenesis and Therapeutic Resistance

Sunaga,

Miura,

Masuda

et al. 2024

Cancers

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Epidermal growth factor (EGF) signaling regulates multiple cellular processes and plays an essential role in tumorigenesis. Epiregulin (EREG), a member of the EGF family, binds to the epidermal growth factor receptor (EGFR) and ErbB4, and it stimulates EGFR-related downstream pathways. Increasing evidence indicates that both the aberrant expression and oncogenic function of EREG play pivotal roles in tumor development in many human cancers, including non-small cell lung cancer (NSCLC). EREG overexpression is induced by activating mutations in the EGFR, KRAS, and BRAF and contributes to the aggressive phenotypes of NSCLC with oncogenic drivers. Recent studies have elucidated the roles of EREG in a tumor microenvironment, including the epithelial–mesenchymal transition, angiogenesis, immune evasion, and resistance to anticancer therapy. In this review, we summarized the current understanding of EREG as an oncogene and discussed its oncogenic role in lung tumorigenesis and therapeutic resistance.

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“…Ovarian xenograft tumour model [170]. Triple negative breast cancer [171] A9(B8) Humanised mouse IgG2 antibody NSCLC with erlotinib/ gefitinib [172].…”

Section: D1(a12)mentioning

confidence: 99%

Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing

Reed

Ager

2022

Pathogens

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Influenza A virus (IAV) infection is a global public health burden causing up to 650,000 deaths per year. Yearly vaccination programmes and anti-viral drugs currently have limited benefits; therefore, research into IAV is fundamental. Leukocyte trafficking is a crucial process which orchestrates the immune response to infection to protect the host. It involves several homing molecules and receptors on both blood vessels and leukocytes. A key mediator of this process is the transmembrane glycoprotein L-selectin, which binds to vascular addressins on blood vessel endothelial cells. L-selectin classically mediates homing of naïve and central memory lymphocytes to lymph nodes via high endothelial venules (HEVs). Recent studies have found that L-selectin is essential for homing of activated CD8+ T cells to influenza-infected lungs and reduction in virus load. A disintegrin and metalloproteinase 17 (ADAM17) is the primary regulator of cell surface levels of L-selectin. Understanding the mechanisms that regulate these two proteins are central to comprehending recruitment of T cells to sites of IAV infection. This review summarises the immune response to IAV infection in humans and mice and discusses the roles of L-selectin and ADAM17 in T lymphocyte homing during IAV infection.

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Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI–Mediated Anticancer Activity in NSCLC

Cited by 10 publications

References 32 publications

Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Association of Polymorphisms in Inflammation Genes With the Prognosis of Advanced Non-Small Cell Lung Cancer Patients Receiving Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Role of Epiregulin in Lung Tumorigenesis and Therapeutic Resistance

Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing

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