Advancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin

Shih Yao Chen, Chung Teng Wang, Tang Hsiu Huang, Jeng Liang Tsai, Hao Tien Wang, Yi Ting Yen, Yau Lin Tseng, Chao-Liang Wu, Jia Ming Chang, Ai-Li Shiau

研究成果: Article同行評審

摘要

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells’ vulnerabilities, potentially marking a significant advancement in managing this deadly disease.

原文English
文章編號1597
期刊Cells
13
發行號18
DOIs
出版狀態Published - 2024 9月

All Science Journal Classification (ASJC) codes

  • 一般生物化學,遺傳學和分子生物學

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