Repurposing the Antiparasitic Agent Praziquantel for Breast Neoplasm Therapy: A Narrative Review of the Mechanistic Rationale, Current Evidence and Translational Barriers

Background: Drug repurposing has become an established route into oncology because agents with a mature safety, pharmacokinetic and manufacturing record can be advanced faster and at lower cost than new chemical entities. Praziquantel, the mainstay of antischistosomal therapy for more than four decades, has been proposed as one such candidate. Aim: This narrative review examines the case for repurposing praziquantel in breast neoplasia and does so critically rather than promotionally. Results: Three strands of mechanistic rationale are identified: Praziquantel's target in the parasite is a TRPM channel, raising the untested hypothesis that it might also target the related human TRPM channels linked to breast tumour proliferation, migration and chemoresistance; the R-enantiomer is a partial agonist at the human 5-HT2B receptor, a node in a serotonergic pathway with documented roles in mammary tumour biology; and praziquantel has been proposed to lower the apoptotic threshold of carcinoma cells through down-regulation of the X-linked inhibitor of apoptosis protein which could improve the effects of cytotoxic chemotherapy. Against this rationale, the experimental evidence is limited. No study designed to evaluate praziquantel in a breast cancer model was identified. The syntheses that studied the praziquantel chemosensitising effect in combination with paclitaxel did not show direct antineoplastic activity as monotherapy; a single recent paper reported a monotherapy effect of praziquantel on hepatoma lines, but this has not been tested in breast cancer. A substantial exposure gap separates the concentrations at which activity is reported in vitro from those achievable clinically, given a systemic bioavailability below 20 per cent, a plasma half-life of one to three hours and approximately 80 per cent albumin binding. The favourable tolerability record derives from single-dose mass administration rather than chronic dosing alongside cytotoxic therapy. Conclusion: We conclude that praziquantel is at present a hypothesis rather than a candidate in breast oncology, and we set out the specific studies that would be required to change that assessment.