Precision prevention: A focused response to shifting paradigms in healthcare

Abstract

Human health and disease are defined at the intersection of molecules, environment, and lifestyle, which combined determine phenotypic outcomes. To date, most clinical applications in the precision medicine space have focused on DNA, with lesser attention given to the biology encoded by RNA molecules, or the complexity of biological regulation at the level of proteins and metabolites. The totality of this information must be integrated in ways that allow for implementation of knowledge-based health promotion and prevention strategies that can help address current limitations in healthcare delivery. This review describes recent advances in the development of diagnostic tools for early detection and stratification of individuals suffering from chronic obstructive pulmonary disease and their heightened risk for the development of lung malignancies. Impact statement The study of LINE-1 retroelements and their role in the pathogenesis of diseases of the lung such as COPD and lung cancer may provide valuable diagnostic and therapeutic tools to identify pre-emptively individuals at risk of pulmonary disease progression. Limited information is presently available on the role of LINE-1 in the regulation of disease phenotypes and the development of novel therapeutics designed to curtail LINE-1-mediated pathogenesis. Successful implementation of precision prevention strategies may help to spare those impacted by obstructive pulmonary disease from continued deterioration, while realizing significant cost savings and improved quality of healthcare.

Long Interspersed Nuclear Element-1 Analytes in Extracellular Vesicles as Tools for Molecular Diagnostics of Non-Small Cell Lung Cancer

“…Active LINEs are a source of endogenous mutagenesis, with reactivation in somatic cells causing a variety of genetic alterations, including aberrant splicing, exon skipping, gene fusions, and genome rearrangements that alter gene expression and cause genome instability [8][9][10]. Furthermore, LINE-1 reactivation creates a positive feedback loop that perpetuates the aberrant behavior of cells carrying mutations in tumor suppressor genes and/or oncogenes [11]. LINE-1 oncogenicity can also involve signaling pathways that are independent of retrotransposition [12].…”