Researchers from Canada have published a review which summarizes recently established and emerging signalling pathways that may influence the next generation of targeted pulmonary arterial hypertension therapies. They note that the therapeutic landscape for this condition is moving towards mechanism-based approaches with the potential to alter the course of the disease. In particular, the transforming growth factor-β (TGF-β) superfamily has come to the fore as a fourth major therapeutic pathway. Agents targeting this pathway — such as sotatercept, an activin signalling inhibitor — have shown meaningful clinical and haemodynamic benefits in large randomised clinical trials. Other promising avenues include receptor tyrosine kinases — notably platelet-derived growth factor receptor signalling — as well as hypoxia-related and metabolic reprogramming pathways. There is also growing evidence for the role of immune dysregulation, hormonal and neurohormonal signalling, and epigenetic, genetic, and cell-cycle abnormalities in the pathogenesis of pulmonary arterial hypertension.
The authors conclude that ongoing translational research and forthcoming clinical trials will be critical to identifying the right patients, refining treatment strategies, and establishing both the short- and long-term impact of these therapies on clinical outcomes and survival.
Read more at this link (abstract only) on Current Opinions in Pulmonary Medicine
Citation
Budhram B, Bonnet S, Weatherald J. Promising signalling pathways for the treatment of pulmonary arterial hypertension. Curr Opin Pulm Med. 2026 May 5. doi: 10.1097/MCP.0000000000001278. Epub ahead of print. PMID: 42083394.