Inhibition of checkpoint kinase prevents human oocyte apoptosis induced by chemotherapy and allows enhanced tumour chemotherapeutic efficacy.

This article investigates the impact of taxane and platinum (TP) chemotherapy on human ovarian reserve and explores whether inhibition of checkpoint kinase (CHEK) pathways can protect human oocytes during chemotherapy while enhancing anti-tumour effects. The study found that TP chemotherapy reduces ovarian reserve by inducing apoptosis of primordial follicles via activation of the CHEK-TAp63α pathway, with platinum (cisplatin) causing more damage than taxane (paclitaxel). Using human ovarian tissue cultures and a novel mouse model combining human ovarian xenotransplantation with patient-derived tumour xenografts, the researchers demonstrated that CHEK1 and CHEK2 inhibitors prevent chemotherapy-induced oocyte apoptosis and simultaneously increase cisplatin’s anti-tumour efficacy. These findings suggest that CHEK1/2 inhibitors hold potential as pharmacological agents for fertility preservation in female cancer patients undergoing chemotherapy, though clinical validation and long-term safety assessments remain necessary.