Epidermal growth factor receptor (EGFR) inhibitory monoclonal antibodies and EGFR tyrosine kinase inhibitors have distinct effects on the keratinocyte innate immune response

Ommori, Rie; Park, K.; Miyagawa, Fumi; Azukizawa, Hiroaki; Kanno, Masatoshi; Asada, Hideo

doi:10.1111/bjd.15445

Cited by 5 publications

(1 citation statement)

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“…In recent years, more attention has been paid to the relationship between EGFR and the development of lung carcinoma, and EGFR-TKIs targeting EGFR have been widely applied for the treatment of advanced lung carcinoma [ 9 ]. Osimertinib is the 3 rd generation of EGFR-TKIs and the only agent used for the treatment of NSCLC patients with EGFR T790M positive mutations [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

AZD3759 enhances radiation effects in non-small-cell lung cancer by a synergistic blockade of epidermal growth factor receptor and Janus kinase-1

Zhao¹,

Mao

et al. 2021

Bioengineered

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AZD3759 is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on the basis of gefitinib and has been proven to enter the central nervous system. Although the promising antitumor effects of AZD3759 on non-small cell lung cancer (NSCLC) have been demonstrated in clinical trials, the regulatory effects of this inhibitor on the antitumor efficacy of radiation (RA) are unclear. The present study aimed to compare the effects of AZD3759 and osimertinib on RA efficacy in NSCLC and explore the potential mechanism of action of AZD3759. We found that the survival in RA-treated NSCLC cells was significantly decreased by treatment with 500 nM AZD3759 and osimertinib at the RA dosage of 8 Gy. The apoptotic rate, cell cycle arrest, and DNA damage in RA-treated NSCLC cells and brain metastasis in RA-treated xenograft nude mice were significantly enhanced by the co-administration of AZD3759 and osimertinib, respectively. In addition, AZD3759 showed a significantly stronger efficacy than osimertinib did. Mechanistically, the receptor tyrosine kinase signaling antibody array revealed that Janus kinase-1 (JAK1) was specifically inhibited by AZD3759, but not by osimertinib. The effects of AZD3759 on RA efficacy in PC-9 cells and in a brain metastasis animal model were significantly abolished by the overexpression of JAK1. Collectively, our results suggested that AZD3759 promoted RA antitumor effects in NSCLC by synergistic blockade of EGFR and JAK1.

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Section: Introductionmentioning

confidence: 99%