Is endothelin targeting finally ready for prime time?

Area of Science:

• Endocrinology
• Pharmacology
• Cardiovascular Medicine

Background:

• The endothelin peptide family regulates vital biological functions and is implicated in various diseases.
• Endothelin receptor antagonism (ERA) faced clinical translation challenges due to side effects like fluid retention.

Purpose of the Study:

• To review recent advancements in endothelin targeting strategies.
• To highlight the expanding clinical applications and ongoing research for endothelin receptor antagonists (ERAs).

Main Methods:

• Review of current literature on endothelin pathophysiology and ERA clinical trials.
• Analysis of emerging therapeutic strategies, including combination therapies and novel antibody-based approaches.

Main Results:

• Favorable results in recent trials have expanded ERA indications to resistant arterial hypertension and glomerulopathies.
• Ongoing studies explore ERA combinations for fluid retention and solid tumors, with antibody-based therapies under investigation.

Conclusions:

• Improved understanding and new ERA development are revitalizing clinical translation.
• Endothelin targeting strategies show potential for broader clinical application, overcoming previous limitations.