Strategies targeting angiogenesis in advanced non-small cell lung cancer
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Jun Wang1,*, Jianpeng Chen2,*, Yan Guo3, Baocheng Wang1 and Huili Chu1
1 Department of Oncology, General Hospital, Jinan Command of the People’s Liberation Army, Jinan, China
2 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
3 Department of Outpatient, Military Command of Shandong Province, Jinan, China
* These authors have contributed equally to this work
Jun Wang, email:
Keywords: NSCLC, angiogenesis, antiangiogenic agents, bevacizumab
Received: January 06, 2017 Accepted: April 27, 2017 Published: May 17, 2017
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy. Numerous oral multitargeting angiogenic small molecule tyrosine kinase inhibitors (TKIs) have been widely evaluated in advanced NSCLC, but only nintedanib in combination with platinum-based doublet chemotherapy has demonstrated a survival benefit in the second-line setting. Additionally, small-molecule TKIs remain the standard of care for patients with mutated EGFR, ALK or ROS1. Moreover, immune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) are changing the current strategy in the treatment of advanced NSCLC without driver gene mutations. The potential synergistic activity of antiangiogenic agents and TKIs or immunotherapy is an interesting topic of research. This review will summarize the novel antiangiogenic agents, antiangiogenic monotherapy, as well as potential combination therapeutic strategies for the clinical management of advanced NSCLC.
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