Emerging Research Directions

Despite advances, several challenges remain:

Resistance and Non-Responders: Some patients show limited improvement, indicating heterogeneity in endothelin receptor function.

Biomarker Development: Identifying reliable biomarkers of endothelin activity could personalize ERA therapy.

Next-Generation Therapies: New approaches, such as RNA interference (RNAi), monoclonal antibodies, and gene therapy, aim to modulate endothelin signaling more precisely.

Preclinical Models: Advanced platforms like organ-on-chip pulmonary systems and 3D vascular models are enabling researchers to dissect receptor-specific mechanisms under physiologically relevant conditions.