Background: Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing
lung disease and is caused by excessive lung scarring. IPF-associated severe mortality
can be attributed to late diagnosis due to its generic symptoms, and more importantly due
to the lack of effective therapies available. Despite extensive research in the past decades,
lung transplant still remains the most effective treatment for IPF. Though two drugs recently
approved by FDA, Pirfenidone and Nintedanib, have shown an ability to reduce the progression
of disease. However, they have shown minimal survival benefits to patients.
Methods: IPF is a multifaceted disorder with poorly understood pathophysiology. We believe
that there are better therapeutic targets veiled in IPF pathophysiology, exploitation of
which may improve current therapeutic approaches to the disease. We have performed an
extensive literature search using several bibliographic databases for peer reviewed articles
discussing molecular targets/pathways involved in the pathogenesis of the disease. Furthermore,
studies involving exploitation of these therapeutic targets and potential therapeutic
agents were identified.
Results: Recently, new and promising targets have been revealed from GWA studies and genetic
microarrays of IPF patients. In this review, we discuss the efficacy and feasibility of
several novel molecular targets including Semaphorin (SEMA) 7A, connective tissue
growth factor, integrin αvβ6, caveolin-1, let 7-d, calcium activated potassium channel
KCa3.1, matrix metalloproteinase-19, lysocardiolipin acetyltransferase, dimethylarginine
dimethylaminohydrolase, and transglutaminase 2. These targets have all shown the potential
to modulate IPF pathophysiology, thereby inhibiting disease progression.
Conclusion: Information gained from this review will be valuable to this field, enabling the
design and development of novel therapeutics for IPF.