Plogosertib Shows Promise in Biliary Tract Cancer with BUBR1 as Potential Biomarker
DENVER, Colo., Aug 05, 2025 (247marketnews.com)- Cyclacel Pharmaceuticals (NASDAQ:CYCC) reported encouraging findings from a recently published independent preclinical study evaluating its PLK1 inhibitor, plogosertib, in biliary tract cancer (BTC) titled Evaluation of antitumor effects of plogosertib, PLK1 inhibitor in biliary tract cancer with BUBR1 as a potential biomarker, which was published in Cancer Research and previously presented at the American Association for Cancer Research (AACR) 2025 Annual Meeting.
Researchers found that multiple BTC cell lines were sensitive to plogosertib, both as a monotherapy and in combination with other agents. In line with its antimitotic mechanism, plogosertib induced mitotic checkpoint complex (MCC) formation in prometaphase, triggering mitotic arrest and ultimately leading to apoptosis in BTC cells.
Importantly, the study identified BUBR1, a mitotic checkpoint protein, as a potential biomarker of response to plogosertib. BTC cells with high BUBR1 expression were notably more sensitive to the PLK1 inhibitor compared to those with lower levels. Furthermore, when combined with an ATR inhibitor, plogosertib demonstrated synergistic antitumor activity in BTC models with elevated BUBR1, suggesting a rational path forward for biomarker-driven combination therapy strategies.
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