No one left behind: review of precision medicine and cystic fibrosis—how the changing approach to cystic fibrosis treatment might lead to tailored therapies for all

Abstract

Cystic fibrosis is an autosomal recessive, multisystem disorder that has been historically associated with poor life expectancy. Due to the defective cystic fibrosis transmembrane conductance regulator protein, patients with cystic fibrosis develop viscous secretions that are difficult to clear, resulting in numerous abnormalities such as chronic airway obstruction, maldigestion and malabsorption. While our understanding of the pathophysiology and disease management have improved, pulmonary disease remains the leading cause of morbidity and mortality in patients with cystic fibrosis. However, since the introduction of precision medicine, novel therapeutic agents have been developed to target the underlying defective protein, resulting in improved disease management and life expectancy. The goal of precision medicine is to provide timely diagnosis, phenotyping, and personalized treatments, based on an individualized analysis of a patient's genome. This article reviews current and potential precision medicine treatments for patients with cystic fibrosis, including cystic fibrosis transmembrane conductance regulator modulators and other modulators designed for patients who would not benefit from currently available therapies. We will also discuss other investigational treatment modalities, such as ribosomal read-though agents and RNA therapy, which may continue the advancement of cystic fibrosis treatment. Current research into methods aimed to better predict patients' responses to personalized treatment, such as theratyping, will also be discussed. Given the benefits of applying precision medicine in cystic fibrosis, future research in this therapeutic approach will also likely benefit other life-threatening monogenetic disorders.