Pulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease with a high mortality rate. PAH manifests by proliferation/apoptosis imbalance of pulmonary vascular cells leading to remodeling of small pulmonary arteries (PA), increased PA pressure, elevated right ventricular afterload, right heart failure and death. Emerging evidence from many research groups indicates that PAH may be viewed as a proliferative disease with a cancer-like nature and shares an incredible number of pathogenic signaling mechanisms with human cancers. This offers exciting opportunity to employ certain cancer-specific strategies as well as re-purpose anti-cancer agents for treatment of PAH. In this review, we discuss various signal transduction pathways that act as "central signaling hubs" in PAH and cancer, particularly those that have a crucial role in driving pulmonary vascular cell proliferation and survival, summarize recent progress in cellular, pre-clinical and clinical studies focused on proliferative/anti-apoptotic component, and discuss the opportunities for re-purposing or cross-development of anti-cancer agents that can be used in improving PAH care. .
- Pullamsetti, S. S.; Savai, R.; Seeger, W.; Goncharova, E. A.
Keywords
- cancer
- molecular mechanisms
- proliferation
- pulmonary arterial hypertension
- treatment
