Cyclacel Pharmaceuticals Reports Promising Preclinical Data for Plogosertib in Treating Biliary Tract Cancer

Cyclacel Pharmaceuticals reported positive preclinical results for plogosertib in treating biliary tract cancer (BTC). The study suggests that BUBR1 protein may serve as a biomarker for plogosertib's effectiveness. PLK1 inhibition shows promise for BTC treatment strategies. The drug operates through its antimitotic mechanism by promoting mitotic arrest and apoptosis of BTC cells.

Cyclacel Pharmaceuticals, Inc. has announced promising preclinical data demonstrating the efficacy of plogosertib, a novel PLK1 inhibitor, in treating biliary tract cancer (BTC). The study, titled "Evaluation of antitumor effects of plogosertib, PLK1 inhibitor in biliary tract cancer with BUBR1 as a potential biomarker," was published in the journal Cancer Research and presented at the American Association of Cancer Research 2025 annual meeting [1].

The preclinical study found that several BTC cancer cell lines were sensitive to plogosertib both as a monotherapy and in combination with other therapies. Consistently with its antimitotic mechanism of action, plogosertib promoted mitotic checkpoint complex (MCC) formation in prometaphase, leading to mitotic arrest and subsequent apoptosis of BTC cells [2].

Significantly, the study identified BUBR1, a critical mitotic checkpoint protein, as a potential biomarker for assessing plogosertib's effectiveness. BTC cells with high BUBR1 expression were found to be more sensitive to plogosertib compared to those with low expression. The study concluded that targeting PLK1, especially in combination with an ATR inhibitor, could be an effective strategy for BTC treatment, particularly when informed by BUBR1 expression levels [1].

Biliary tract cancer (BTC), also known as cholangiocarcinoma, is a rare but aggressive cancer with a poor prognosis. According to the National Cancer Institute’s SEER database, the annual US incidence of BTC is 4.4 per 100,000, and the 5-year overall survival rate is approximately 10–40% even after surgical tumor resection [2]. Current treatment strategies, including chemotherapy, surgery, radiation, and targeted medicines, are not curative, highlighting the urgent need for new, effective treatments.

PLK1 overexpression correlates with poor patient prognosis in several tumors, including BTC, making it a promising target for cancer therapy. Plogosertib, a selective and potent PLK1 inhibitor, has demonstrated impressive efficacy in human tumor xenografts at nontoxic doses. Cyclacel's translational biology program supports the development of plogosertib in solid tumors and leukemias [1].

The preclinical data suggest that plogosertib may be effective in KRAS-mutated metastatic colorectal cancer and other cancers associated with specific genetic mutations. Initial dose escalation data from a Phase 1 clinical study of oral plogosertib indicate that the compound is well-tolerated with no dose-limiting toxicity observed in multiple dosing schedules, and clinical benefit was observed in patients with various cancer types, including adenoid cystic, biliary tract, ovarian, and squamous cell sinus cancers [1].

Cyclacel Pharmaceuticals is a clinical-stage biopharmaceutical company developing innovative cancer medicines based on cell cycle and mitosis biology. The company's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications [2].

References:

[1] https://www.marketscreener.com/news/cyclacel-pharmaceuticals-inc-announces-preclinical-data-showing-that-cannabis-of-the-biliary-tract-ce7c5edbd18ff122
[2] https://www.biospace.com/press-releases/cyclacel-pharmaceuticals-highlights-preclinical-data-showing-that-cancer-of-the-biliary-tract-is-sensitive-to-plogosertib