Introduction: Distal pulmonary arterial remodeling in pulmonary arterial hypertension (PAH) is driven by abnormal proliferation of endothelial cells, smooth muscle cells, and fibroblasts, coupled with apoptosis resistance and impaired bone morphogenetic protein receptor-2 (BMPR2) signaling. Growth factor pathways such as platelet-derived growth factor (PDGF) further promote vascular remodeling. These insights support the view of PAH as a cancer-like-disease and highlight the potential of emerging targeted therapies, including Transforming growth factor-beta (TGF-β) and PDGF receptor inhibitors, to move beyond vasodilation toward true disease-modifying strategies.
Areas covered: This article examines the concept of PAH as a cancer-like disease, emphasizing shared pathological mechanisms such as unchecked cellular proliferation, apoptosis resistance, genomic instability, and dysregulated growth factor signaling, mirroring oncogenic processes. Evidence from preclinical studies and clinical trials underscores that targeting these cancer-like mechanisms can attenuate vascular remodeling.
Expert opinion: The discovery of novel signaling pathways - such as the TGF-β superfamily, growth factors, and tyrosine kinases - has advanced the understanding of PAH and opened opportunities for disease-modifying therapies. Targeting these pathways, including BMPR2 restoration, TGF-β inhibition, and tyrosine kinase blockade, has shown encouraging results beyond the vasodilator-focused standard of care. These innovations may reshape PAH management by improving outcomes, and potentially altering disease progression.
Keywords: BMPR2; PAH; Sotatercept; TGF-β; growth factors; proliferation; tyrosine-kinase inhibitor.