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23.11.2019 | PRECLINICAL STUDIES

Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug Z_HER2:V2-pemetrexed in lung adenocarcinoma Xenografts

verfasst von: Jingya Han, Yan Zhao, Xinming Zhao, Tuo Ma, Tiancheng Hao, Jiahui Liu, Zhaoqi Zhang, Jingmian Zhang, Jianfang Wang

Erschienen in: Investigational New Drugs | Ausgabe 4/2020

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Summary

Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate Z_HER2:V2-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using Z_HER2:V2-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the ^99mTc-labeled Z_HER2:V2-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with ^99mTc-Z_HER2:V2-pemetrexed demonstrated that in HER2+ A549 models, Z_HER2:V2-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that Z_HER2:V2-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the Z_HER2:V2-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the Z_HER2:V2-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the Z_HER2:V2-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma.

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Titel: Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts
verfasst von: Jingya Han
Yan Zhao
Xinming Zhao
Tuo Ma
Tiancheng Hao
Jiahui Liu
Zhaoqi Zhang
Jingmian Zhang
Jianfang Wang
Publikationsdatum: 23.11.2019
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 4/2020
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00876-3

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Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug Z_HER2:V2-pemetrexed in lung adenocarcinoma Xenografts

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