Luteinizing Hormone-Releasing Hormone (LHRH)-Targeted Treatment in Ovarian Cancer

Ovarian cancer remains one of the most lethal gynecologic malignancies and requires more effective and targeted treatment strategies. Luteinizing hormone-releasing hormone (LHRH), or gonadotropin-releasing hormone (GnRH), receptors are expressed in approximately 80% of ovarian tumors, representing a promising target for targeted drug delivery. This narrative review aimed to explore the development and advancements of LHRH-receptor targeted therapies in ovarian cancer. A bibliographic search was performed using PubMed, Scopus, Google Scholar, and Web of Science. The search strategy included studies on LHRH-peptide drug delivery systems and LHRH-conjugate nanosystems. Literature search covered in vitro studies, preclinical models, and ongoing clinical trials from 2000 to 2025. A total of 19 studies were included for peptide-drug delivery, and 30 studies were included for LHRH-conjugated nanosystems. Overall findings demonstrated enhanced preclinical efficacy, achieving ~50-80% tumor-growth inhibition and 2-4-fold higher cellular uptake, alongside reduced systemic toxicity. Early clinical studies, although limited, reported an overall response/disease-control rate of approximately 50%, supporting improved tumor accumulation of drugs, small interfering RNA (siRNA), and diagnostic agents. Ovarian cancer-specific therapy, targeting LHRH receptors, represents a promising strategy to enhance therapeutic outcomes. Further efforts in preclinical and clinical research are essential to refine personalized treatments and integrate them with a combination of therapies.