Camptothecin and cervical cancer: Mechanistic insights, therapeutic potential, and clinical advancements

Camptothecin (CPT) and its analogues are a class of anticancer drugs with vast therapeutic potential in the treatment of cervical cancer. The CPT analogues are effective topoisomerase I inhibitors, interfering with DNA replication by blocking re-ligation, producing DNA damage, cell cycle arrest, and apoptosis. The mechanism involves permeability changes of the mitochondrial membrane, cytochrome c release, and caspase activation. Camptothecin (CPT) and its analogues have unique mechanistic anticancer activity via the inhibition of topoisomerase I, but as single agents, they have currently of limited clinical activity because of toxicity, insolubility, and modest response rates in cervical carcinoma. Nonetheless, the clinical activity of the semi-synthetic analogues irinotecan and topotecan in advanced and recurrent cervical cancer has been described with response rates of 13–26 %. Recent studies have been aimed at new drug delivery mechanisms like nanoparticles for increasing stability, bioavailability, and tumour-targeted drug delivery. Combining chemotherapy with CPT analogues with conventional chemotherapy, radiotherapy, and immunotherapy has also emerged with the potential to increase cure rates. Management of toxicity continues to be a challenging task, with efforts being made to minimize toxicities without compromising therapeutic benefits. Future directions like biomarker-guided selection of patients and personalized treatment hold the promise to optimize the efficacy of CPT-based therapies. In the present review, mechanism of action of CPT, clinical trials with CPT, and future therapeutic concepts for the treatment of cervical cancer has been discussed. Future advances should aim at simplifying drug delivery systems, rationally combining drugs and the identification of predictive biomarkers for precision medicine. An improved understanding of these aspects will be pivotal in bridging CPT-based therapy to effective and safe clinical application in cervical cancer.