The Role of IGF-Pathway Biomarkers in Determining Risks, Screening, and Prognosis in Lung Cancer: A Systematic Review.

Abstract

Background: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and the highest rates of annual cancer deaths in the U.S. Currently, age and smoking history are the primary factors that qualify patients for low-dose computed tomography (LDCT) screening, which contributes heavily to a high false discovery rate. This limitation to the current screening paradigm has prompted research to identify biomarkers that will help more clearly define eligible patients for LDCT screening, differentiate indeterminate pulmonary nodules, and select individualized cancer therapy. Biomarkers within the Insulin-like Growth Factor (IGF) family have come to the forefront of this research. Methods: Literature available through PubMed and Google Scholar sources was cataloged using keywords: {Lung Cancer} AND {IGF} AND {Risk OR Diagnosis OR Prognosis OR Prognostication OR Treatment}. The results were summarized and provided herein.Results: Multiple biomarkers within the IGF family (or axis) have been investigated, most notably IGF-I and IGF binding protein 3 (IGFBP-3). However, newer studies seek to expand this search to other molecules within the IGF axis. Results have differed, however, due to features such as the pre-disease variable expression of IGF-I and IGFBP-3, likely promoted by factors such as obesity and smoking history. Certain studies have demonstrated these biomarkers are useful as a companion test alongside lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias from pre-analytical variables and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent application of treatment via systemic therapy. Despite these advances, however, additional knowledge as to the intricacies of regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic tests and to identify novel targets for therapeutic intervention. Conclusions: The IGF system likely plays a role in multiple phases of lung cancer; however, there is a surplus of conflicting data, especially prior to development of the disease and during early stages of detection. IGF biomarkers may be valuable in the screening, prognosis, and treatment of lung cancer, though their exact application requires further study.