PARP inhibitor olaparib induces DNA damage and acts as a drug sensitizer in an in vitro model of canine hematopoietic cancer

Background The introduction of genetic tests based on next-generation sequencing techniques into veterinary cancer diagnostics provides information on molecularly targeted therapies useful for dogs. However, there is still a lack of in vitro studies describing the effect and mechanism of action of such anticancer drugs in companion animals. Our study aimed to demonstrate in vitro activity of a commonly used PARP inhibitor, olaparib, in canine lymphoma and leukemia cells as well as to indicate its potential uses in anti-cancer therapy based on the mutational status of DNA damage related genes. Canine lymphoma and leukemia cell lines were incubated with olaparib alone and in combination with doxorubicin, and the impact of a single drug and combinations on cell viability, proliferation, induction of apoptosis, and DNA damage were assessed. Results The study showed that olaparib acts as a single agent and also as a chemosensitizer, due to its ability to potentiate cytotoxic effects of doxorubicin. Conclusions Olaparib may be an interesting oral therapy alternative to classic chemotherapy in dogs with known DNA repair disorders and may also be effective in adjuvant therapy due to its synergistic effect with doxorubicin.