Topoisomerase inhibitors in cervical cancer: mechanistic insights and therapeutic strategies

Cervical cancer represents a critical global health burden, particularly among women in countries with limited healthcare infrastructure, where it accounts for a substantial proportion of cancer-related morbidity and mortality. It remains highly prevalent in developing regions. Most cervical cancers are squamous cell carcinomas originating from the cervix lining cells, mainly because of chronic infection with high-risk human papillomaviruses (HPV) types. Additionally, the likelihood of infection is enhanced by behaviours include early sexual activity, multiple partners, smoking, and immunosuppression. Topoisomerases, vital enzymes for DNA replication and transcription are crucial for therapeutic intervention in cancer. Inhibitors of Topoisomerase I and II, such as camptothecin derivatives (topotecan, irinotecan) and drugs like etoposide and daunorubicin, have shown effectiveness in treating cancers, including cervical cancer, by stabilizing topoisomerase-DNA complexes and inducing lethal DNA strand breaks. However, traditional treatments like chemotherapy and radiation often have high toxicity and limited survival benefits. The development of new topoisomerase inhibitors with better efficacy and safety is essential. Advances in tumour biology have led to multi targeting drugs that target multiple cancer cells survival pathways, offering a more comprehensive anti-cancer effect. This review explores the application of topoisomerase inhibitors in advanced and recurrent stages of cervical cancer, both as standalone agents and in combination therapies. Combining topoisomerase inhibitors with other treatment options has been used as a strategy to improve therapeutic outcomes. Additionally new therapeutic strategies like nanoformulations, antibody drug conjugates, and biomarker-based therapies lead to effective therapeutic outcomes in cervical cancer treatment. Ongoing research and development in this area are crucial for enhancing cervical cancer treatment.