Drug repurposing in gynaecological cancers: Proven drugs for new challenges

Gynaecological malignancies, including cervical, endometrial, ovarian, vaginal and vulval cancers, pose therapeutic challenges that contribute to this group being the third most frequent cause of cancer-related deaths globally in women. While advances have been made in both screening for cervical cancer and immunisation against human papillomavirus strains in some countries, other gynaecological cancers have not seen improvements in early screening and prevention strategies. Drugs inhibiting poly (ADP-ribose) polymerase (PARP) have been incorporated into the clinical management of homologous recombination-deficient ovarian cancers, including as maintenance therapies post-surgery; however, these constitute only around half of all ovarian cancers. Developing new therapeutic options for all gynaecological malignancies, including those that demonstrate innate or acquired resistance to standard-of-care chemotherapeutic regimens, remains a challenge. Drug repurposing, defined as the repositioning of drugs that have been approved for the treatment of specific indications to treat other conditions, demonstrates strong potential for the clinical management of gynaecological malignancies. This review highlights diverse drug repurposing approaches applied to gynaecological cancers. Examples include computational methods such as disease and drug signature matching, network or pathway mapping, genetic association studies, drug similarity networks, molecular docking, machine learning, and serendipitous clinical observations. High-throughput compound library and drug-based phenotypic screening also contribute to candidate identification. Repurposed drugs with established safety and pharmacological profiles can accelerate therapeutic discovery; however, some regulatory and industry barriers remain. Coupled with advanced patient-centred technologies, 3D tumoroids, tumour-on-a-chip, and microfluidic systems, drug repurposing strategies promise to advance personalised medicine and improve survival outcomes for women with gynaecological malignancies.