Peer-reviewed veterinary case report
Verdinexor drug shows activity against canine bone cancer cells
By Breitbach, Justin T et al.·Published in Veterinary and comparative oncology·2021·Department of Veterinary Biosciences, United States·View original on PubMed →
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Original publication title: The selective inhibitor of nuclear export (SINE) verdinexor exhibits biologic activity against canine osteosarcoma cell lines.
- Species:
- dog
Plain-English summary
A study found that a new drug called verdinexor showed promise in treating osteosarcoma, a type of bone cancer, in dogs. Researchers tested it on canine osteosarcoma cell lines and found that it effectively slowed down cancer cell growth, especially when combined with the standard chemotherapy drug doxorubicin. The combination treatment was more effective than doxorubicin alone, suggesting that using verdinexor alongside traditional chemotherapy could improve outcomes for dogs with this cancer. While this research is still in the early stages, it offers hope for better treatment options for dogs diagnosed with osteosarcoma.
People also search for: dog osteosarcoma treatment · verdinexor for dogs · doxorubicin side effects in dogs
Abstract
Verdinexor (KPT-335) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) compound that inhibits the function of the nuclear export protein Exportin 1 (XPO1/CRM1). In the present study, we sought to characterize the expression of XPO1 in primary canine osteosarcoma (OS) tumour samples, OS cell lines and normal osteoblasts and evaluate the in vitro activity of verdinexor alone or in combination with doxorubicin. Canine OS cell lines and a subset of primary OS tumours showed increased XPO1 transcript and protein expression as compared with normal canine osteoblast cells. All canine OS cell lines exhibited dose-dependent growth inhibition and increased caspase 3,7 activity in response to low nanomolar concentrations of verdinexor (ICconcentrations ranging from 21 to 74 nM). Notably, growth inhibition of normal canine osteoblast cell lines treated with verdinexor was observed at high micromolar concentrations (IC = 21 μM). The combination of verdinexor and doxorubicin resulted in potent inhibition of cell viability and demonstrated synergetic activity in three canine OS cell lines. Concordantly, OS cell lines showed increased γH2A.X foci following treatment with doxorubicin and recovery in verdinexor compared with cells treated with doxorubicin and recovered in normal media for 24 hours. These findings demonstrate that verdinexor has biologic activity against canine OS cell lines at physiologically relevant doses and suggest that XPO1 inhibition in combination with standard doxorubicin treatment offers promising potential for chemotherapeutic intervention in canine OS.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/33438820/