Decoding the endothelin-1 network: molecular drivers of ovarian cancer malignancy and new therapeutic horizons

This review provides an in-depth analysis of the key regulatory pathways involving endothelin-1 (ET-1) and its receptors in the progression of ovarian cancer. As one of the most common malignancies affecting the female reproductive system, ovarian cancer exhibits complex pathogenesis and limited treatment options, making it a critical focus in oncology research. ET-1, a potent vasoconstrictive peptide with diverse biological functions, is implicated not only in normal physiological processes but also plays a pivotal role in ovarian cancer initiation, progression, invasion, metastasis, and chemoresistance. The article begins by outlining the fundamental features of ovarian cancer, including its major histopathological subtypes, incidence, and mortality rates. It then examines the structural and functional aspects of ET-1 and its receptors, elucidating their multifaceted roles in ovarian cancer pathobiology, such as promoting tumor cell proliferation, inhibiting apoptosis, inducing angiogenesis, facilitating epithelial-mesenchymal transition (EMT), mediating chemotherapy resistance, and enhancing cell adhesion and invasion. Furthermore, the review highlights the therapeutic potential of targeting ET-1 signaling pathways, encompassing strategies such as inhibition of ET synthesis, receptor antagonism, and combination therapies. Finally, it discusses future research directions aimed at advancing precision medicine approaches for ovarian cancer treatment.