Peer-reviewed veterinary case report
New oral drug KPT-335 shows activity against canine melanoma cells
By Breit, Megan N et al.·Published in BMC veterinary research·2014·View original on PubMed →
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Original publication title: Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines.
- Species:
- dog
Plain-English summary
Researchers tested a new drug called KPT-335 on canine melanoma cells, which are cancer cells found in dogs. They found that KPT-335 effectively stopped the growth of these cancer cells, prevented them from forming colonies, and even caused some of the cells to die. The drug worked by targeting a specific protein involved in cancer progression, leading to increased levels of important tumor suppressor proteins. This suggests that KPT-335 could be a promising treatment option for dogs diagnosed with malignant melanoma in future clinical trials.
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Abstract
BACKGROUND: Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. RESULTS: We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. CONCLUSIONS: KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/25022346/