The mitotic regulator polo‐like kinase 1 as a potential therapeutic target for c‐Myc‐overexpressing canine osteosarcomas

Osteosarcoma is the most common primary malignant bone tumour in dogs, characterized by a locally aggressive and highly metastatic behaviour. Despite the current standards of care, most dogs succumb to the disease, indicating the need for novel treatment strategies. Polo‐like kinase 1 (PLK1) is dysregulated in a variety of human cancer types, including osteosarcoma, and induces c‐Myc accumulation. The crosstalk between the two molecules coordinates cell proliferation, differentiation, self‐renewal and apoptosis. Therefore, PLK1 has recently emerged as a potential therapeutic target, mainly in tumours overexpressing c‐Myc. BI 2536 is a selective PLK1 inhibitor promoting mitotic arrest and apoptosis in a variety of cancer cells. This research aimed at evaluating PLK1 and c‐Myc protein expression in 53 appendicular canine osteosarcoma (cOSA) samples and the in vitro effects of BI 2536 on a c‐Myc and PLK1‐overexpressing cOSA cell line (D17). PLK1 and c‐Myc expression in cOSA samples showed no correlation with clinicopathological data. However, c‐Myc overexpression was associated with a significantly reduced overall survival (p = .003). Western Blot and RT‐qPCR assays revealed that D17 expressed high protein and transcript levels of both PLK1 and MYC. When treated with BI 2536 (range 2.5–15 nM) for 24 h, D17 showed a substantial decrease in cell growth, inducing apoptosis and G(2)/M cell cycle arrest. Interestingly, under BI 2536 treatment, D17 showed decreased c‐Myc protein levels. Consistent with human OSA, these preliminary data outline the prognostic value of c‐Myc expression in cOSA and highlight the potential role of PLK1 as an antiproliferative therapeutic target for tumours overexpressing c‐Myc.