Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer

Lu Wanjun; Liu Lixia; Kang Xiang; Ren Kangkang; Huang Ye; Cheng Minzhang; Li Xiaolei; Xu Fei; Xu Xinping

doi:10.3724/abbs.2024069

Acta Biochimica et Biophysica Sinica (May 2024)

Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer

Lu Wanjun,
Liu Lixia,
Kang Xiang,
Ren Kangkang,
Huang Ye,
Cheng Minzhang,
Li Xiaolei,
Xu Fei,
Xu Xinping

Affiliations

Lu Wanjun: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","The First Clinical Medical College, Nanchang University, Nanchang 30006, China"]
Liu Lixia: ["Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China"]
Kang Xiang: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","The First Clinical Medical College, Nanchang University, Nanchang 30006, China"]
Ren Kangkang: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang 330052, China"]
Huang Ye: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang 330052, China"]
Cheng Minzhang: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang 330052, China"]
Li Xiaolei: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang 330052, China"]
Xu Fei: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang 330052, China"]
Xu Xinping: ["Jiangxi Clinical Research Center for Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China","Jiangxi Hospital of China-Japan Friendship Hospital, Nanchang 330052, China"]

DOI: https://doi.org/10.3724/abbs.2024069
Journal volume & issue: Vol. 56
pp. 1022 – 1033

Abstract

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Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

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