Precision Medicine Approaches for Stratification and Development of Novel Therapies of Latin(x) Patients at Risk of Lung Malignancy

Precision medicine has emerged as an optimal health-care delivery platform, which emphasizes integration of individual patient characteristics into patient care. For lung cancer, precision approaches have focused mostly on targeted therapies directed at tyrosine kinases and immunotherapy. It is proposed that refinements should focus on improved risk stratification of patients at heightened risk of lung malignancy, namely patients with chronic obstructive pulmonary disease (COPD). African ancestry is associated with worsened clinical outcomes in COPD and lung cancer, which is relevant for Latinx populations given that varying degrees of African ancestry exist among several Latinx subgroups. The work reviewed here focuses on ORF1p, a protein encoded by Long Interspersed Element-1 (LINE-1) and associated with genetic instability. Because high expression of ORF1p is associated with poor prognosis in patients with non-small-cell lung cancer (NSCLC), it is hypothesized that circulating ORF1p can be monitored as a proxy of genetic instability in patients with COPD and lung cancer. Circulating ORF1p levels correlate with FEV1 deficits and airflow limitation (the hallmark of COPD) in former smokers, and tissue expression of ORF1p is increased in TP53 mutant NSCLC compared to wildtype. Understanding the role of ORF1p in COPD and lung cancer and its utility as a biomarker of genetic instability may lead to advances in lung cancer care and development of novel targeted therapies.