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...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-01, Vol.22 (3), p.1395
Main Authors: Mattiello, Luca, Pucci, Giulia, Marchetti, Francesco, Diederich, Marc, Gonfloni, Stefania
Format: Article
Language:English
Subjects:
Abl protein
Adjuvants
Allosteric properties
allosteric tyrosine kinase inhibitors
asciminib
BCR-ABL protein
Breast cancer
Cancer therapies
Cell cycle
Chemotherapy
Cyclophosphamide
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA damage
DNA damage response
drug repurposing
Enzyme inhibitors
Fertility
Follicles
Fusion protein
Hematology
Hypotheses
Infertility
Kinases
Ovarian cancer
ovarian reserve
Ovaries
Patients
Phosphorylation
Protein-tyrosine kinase
Quality of life
Tyrosine
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22031395