Asciminib Mitigates DNA Damage Stress Signaling Induced by Cyclophosphamide in the Ovary

Cancer treatments can often adversely affect the quality of life of young women. One of the most relevant negative impacts is the loss of fertility. Cyclophosphamide is one of the most detrimental chemotherapeutic drugs for the ovary. Cyclophosphamide may induce the destruction of dormant follicles while promoting follicle activation and growth. Herein, we demonstrate the in vivo protective effect of the allosteric Bcr-Abl tyrosine kinase inhibitor Asciminib on signaling pathways activated by cyclophosphamide in mouse ovaries. We also provide evidence that Asciminib does not interfere with the cytotoxic effect of cyclophosphamide in Michigan Cancer Foundation (MCF)7 breast cancer cells. Our data indicate that concomitant administration of Asciminib mitigates the cyclophosphamide-induced ovarian reserve loss without affecting the anticancer potential of cyclophosphamide. Taken together, these observations are relevant for the development of effective ferto-protective adjuvants to preserve the ovarian reserve from the damaging effects of cancer therapies.

Automated summary

Cancer treatments can harm the fertility of young women, with cyclophosphamide being particularly detrimental to the ovaries. However, the Bcr-Abl tyrosine kinase inhibitor Asciminib has been shown to protect ovarian reserve from cyclophosphamide-induced damage. Asciminib does not interfere with the cytotoxic effect of cyclophosphamide on cancer cells, making it a potential ferto-protective adjuvant for preserving fertility in cancer patients.