Rationale for targeting VEGF, FGF, and PDGF for the treatment of NSCLC

Abstract

Lung cancer remains a leading cause of death globally, with the most frequent type, nonsmall cell lung cancer (NSCLC), having a 5-year survival rate of less than 20%. While platinum-based doublet chemotherapy is currently first-line therapy for advanced disease, it is associated with only modest clinical benefits at the cost of significant toxicities. In an effort to overcome these limitations, recent research has focused on targeted therapies, with recently approved agents targeting the epidermal growth factor receptor and vascular endothelial growth factor (VEGF) signaling pathways. However, these agents (gefitinib, erlotinib, and bevacizumab) provide antitumor activity for only a small proportion of patients, and patients whose tumors respond inevitably develop resistance to treatment. As angiogenesis is a crucial step in tumor growth and metastasis, antiangiogenic treatments might be expected to have antitumor activity. Important targets for the development of novel antiangiogenic therapies include VEGF, fibroblast growth factor, platelet-derived growth factor, and their receptors. It is hypothesized that targeting multiple angiogenic pathways may not only improve antitumor activity but also reduce the risk of resistance. Several novel agents, such as BIBF 1120, sorafenib, sunitinib, and cediranib have shown promising preliminary activity and tolerability in Phase II studies, and results of ongoing Phase III randomized studies will be necessary to establish the potential place of these new therapies in the management of individual patients with NSCLC.

Keywords:

• angiogenesis
• vascular endothelial growth factor
• platelet-derived growth factor
• fibroblast growth factor
• tyrosine kinase inhibitor
• nonsmall cell lung cancer

Acknowledgements

This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI). Writing and editorial assistance was provided by Robert Lee, PhD, of MedErgy, which was contracted by BIPI for these services. The authors received no compensation related to the development of the manuscript. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), were fully responsible for all content and editorial decisions, and were involved at all stages of manuscript development.

Dr Chachoua has served on the Speakers Bureau for Eli Lilly, Genentech, and Response Genetics, Inc. Dr Ballas has received past honoraria from Eli Lilly.

Disclosure

The authors report no conflicts of interest in this work.