Peer-reviewed veterinary case report
New treatment targeting ATR kinase for canine lymphoma and leukemia
By Henklewska, Marta et al.·Published in Veterinary and comparative oncology·2024·Department of Pharmacology and Toxicology·View original on PubMed →
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Original publication title: Targeting ATR Kinase as a Strategy for Canine Lymphoma and Leukaemia Treatment.
- Species:
- dog
Plain-English summary
A study tested a new cancer treatment called berzosertib on dog blood cancers like lymphoma and leukemia. Researchers found that berzosertib could kill cancer cells without harming healthy cells, which is promising for treating these conditions. It worked by causing cancer cells to die through a process called apoptosis, which is linked to DNA damage. Additionally, berzosertib showed potential to work well alongside another cancer drug, chlorambucil, by enhancing its effectiveness. While results are encouraging, more research is needed to identify which dogs might benefit the most from this treatment.
People also search for: dog lymphoma treatment options · canine leukemia new therapies · berzosertib for dogs with cancer
Abstract
Ataxia telangiectasia and Rad3-related (ATR) kinase is one of the main regulators of cell response to DNA damage and replication stress. Effectiveness of ATR targeting in human cancers has been confirmed in preclinical studies and ATR inhibitors are currently developed clinically in human oncology. In the presented study, we tested the anticancer efficacy of ATR inhibitor berzosertib in an in vitro model of canine haematopoietic cancers. Using MTT assay and flow cytometry, we assessed the cytotoxicity of berzosertib in four established canine lymphoma and leukaemia cell lines and compared it with its activity against noncancerous canine cells. Further, we estimated the level of apoptosis in berzosertib-treated cells via flow cytometry and assessed H2AX phosphorylation as a marker of DNA damage using western blot technique. In flow-cytometric analysis, we also evaluated potential synergism between berzosertib and chlorambucil and assessed the influence of berzosertib on cell cycle disturbances induced by the drug. The results demonstrated that berzosertib, even without additional DNA damaging agent, can be effective against canine lymphoma and leukaemia cells at concentrations that were harmless for noncancerous cells, although sensitivity of individual cancer cell lines varied greatly. Cell death occurred through caspase-dependent apoptosis via induction of DNA damage. Berzosertib also acted synergistically with chlorambucil, probably by preventing DNA damage repair as a consequence of S-phase arrest abrogation. In conclusion, ATR inhibition may provide a new therapeutic option for the treatment of canine lymphomas and leukaemias, but further studies are required to determine potential biomarkers of their susceptibility.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/39300906/