Synergistic effect of combined PI3K and PLK1 inhibition in anaplastic thyroid carcinoma cells.

e22205 Background: Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer. Despite recent efforts aimed at defining its most common molecular alterations, there is still no effective treatment. PI3K, RAS and BRAF are some of the key driver oncogenic pathways defined by molecular studies. Furthermore, overexpression of PLK1 is extremely common. We evaluated the effect of combining inhibitors of PLK1 and PI3K in PI3K active ATC cell lines. Methods: Cell lines with p53 deletion and PI3K activation were used. Cell viability was evaluated by WST-1 assay after 72 hours treatment. Treatment responses were evaluated using GraphPad software and synergy was evaluated by determining the combination index using ComboSyn software. Results: Treatment with the PLK1 inhibitor BI2536 resulted in significant apoptosis and cell cycle arrest in all ATC cell lines, independent of their driver mutation. However, PI3Khighcells displayed mitotic slippage, suggesting a possible mechanism leading to resistance. C...