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
Affiliations
Shih-Yao Chen
Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan
Chung-Teng Wang
Tong Yuan Diabetes Center, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Tang-Hsiu Huang
Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Jeng-Liang Tsai
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Hao-Tien Wang
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Yi-Ting Yen
Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Yau-Lin Tseng
Division of Thoracic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Chao-Liang Wu
Tong Yuan Diabetes Center, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Jia-Ming Chang
Thoracic Division, Department of Surgery, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan
Ai-Li Shiau
Tong Yuan Diabetes Center, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
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.
