– Biliary tract cancer (BTC) or cholangiocarcinoma is an aggressive tumor with poor prognosis –
KUALA LUMPUR, Malaysia, Aug. 04, 2025 (GLOBE NEWSWIRE) — Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; “Cyclacel” or the “Company”), a biopharmaceutical company developing innovative cancer medicines, highlighted a preclinical study from independent investigators titled, “Evaluation of antitumor effects of plogosertib, PLK1 inhibitor in biliary tract cancer with BUBR1 as a potential biomarker” in the journal, Cancer Research, previously reported in a poster at the American Association of Cancer Research 2025 annual meeting.1 The investigators found that several BTC cancer cell lines were sensitive to plogosertib both as monotherapy and in combinations. Consistently with its antimitotic mechanism of action, plogosertib promoted mitotic checkpoint complex (MCC) formation in prometaphase, which induced mitotic arrest resulting in apoptosis of BTC cells.
The authors have also found that BUBR1, a critical mitotic checkpoint protein, may be useful as a biomarker to assess 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 BTC cells with high BUBR1 expression are sensitive to the PLK1 inhibitor plogosertib that demonstrate synergistic effects when combined with an ATR inhibitor, which suggest that targeting PLK1 could be an effective strategy for BTC treatment, especially with BUBR1 expression as a potential biomarker to inform optimal combination therapies.
About Biliary Tract Cancer (BTC)
BTC, also called cholangiocarcinoma, is a rare but aggressive cancer occurring in the biliary tract, a network of small tubes, or ducts, connecting the liver, gallbladder and small intestine. According to estimates from the National Cancer Institute’s SEER database annual US incidence of BTC is 4.4 per 100,000. Prognosis for BTC patients is poor with 5-year overall survival of approximately 10–40% even after surgical tumor resection.
BTC treatment strategies include chemotherapy, surgery, radiation and targeted medicines depending on location and stage. As these approaches are not curative, there is an urgent, unmet medical need to treat patients with relapsed, refractory and/or unresectable BTC.
About Polo-like Kinase and Plogosertib
Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays a central role in cell division or mitosis. PLK1 is an important regulator of the DNA damage cell cycle checkpoint, mitotic entry and exit, spindle formation and cytokinesis, or cell separation into daughter cells. In general, cancer cells, and in particular KRAS mutated and p53(-) cells, are very sensitive to PLK1 depletion. In contrast normal cells with intact cell cycle checkpoints are less sensitive. Pharmacological inhibition of PLK1 in cancer cells blocks proliferation by prolonged mitotic arrest and induces onset of apoptotic death of such cells.
Plogosertib (formerly CYC140) is a novel, small molecule, selective and potent PLK1 inhibitor. It 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. Preclinical data from independent groups have shown that certain ARID1A- and/or SMARCA-mutated cancers, and cancers associated with DNAJ-PKAc fusions, may benefit from treatment with plogosertib. Additionally, recent data suggest that PLK1 inhibition may be effective in KRAS-mutated metastatic colorectal cancer. PLK1 overexpression correlates with poor patient prognosis in several tumors, including biliary tract, esophageal, fibrolamellar liver, gastric, leukemia, lung, ovarian, and squamous cell cancers, as well as MYC-amplified cancers.
Initial dose escalation data from a Phase 1 clinical study of oral plogosertib suggest that the compound is well tolerated with no dose limiting toxicity observed in five dosing schedules. Clinical benefit was observed in patients with adenoid cystic, biliary tract, ovarian, and squamous cell sinus cancers.
About Cyclacel Pharmaceuticals, Inc.
Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle and mitosis biology. The anti-mitotic program is evaluating plogosertib, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel’s strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit www.cyclacel.com.
Forward-looking Statements
This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended and the Safe Harbor provisions of the US Private Securities Litigation Reform Act of 1995, and encompasses all statements, other than statements of historical fact contained in this press release. These forward-looking statements can be identified by terminology such as “may,” “could,” “will,” “expects,” “anticipates,” “aims,” “future,” “intends,” “plans,” “believes,” “estimates,” “targets,” “likely to”, “understands” and similar statements. These forward-looking statements are based on management’s current expectations. However, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. These statements are neither promises nor guarantees but involve known and unknown risks, uncertainties and other important factors and circumstances that may cause Cyclacel’s actual results, performance or achievements to be materially different from its expectations expressed or implied by the forward-looking statements, including conditions in the U.S. capital markets, negative global economic conditions, potential negative developments resulting from epidemics or natural disasters, other negative developments in Cyclacel’s business or unfavorable legislative or regulatory developments. We caution you therefore against relying on these forward-looking statements, and we qualify all of our forward-looking statements by these cautionary statements.
For a discussion of additional factors that may affect the outcome of such forward-looking statements, see our 2024 annual report on Form 10-K, and in particular the “Risk Factors” section, as well as the other documents filed with or furnished to the SEC by Cyclacel from time to time. Copies of these filings are available online from the SEC at www.sec.gov, or on the SEC Filings section of our Investor Relations website at https://investor.cyclacel.com/sec-filings. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. These forward-looking statements should not be relied upon as representing Cyclacel’s views as of any date subsequent to the date of this press release. All forward-looking statements in this press release are based on information currently available to Cyclacel, and Cyclacel and its authorized representatives assume no obligation to update these forward-looking statements in light of new information or future events. Accordingly, undue reliance should not be placed upon the forward-looking statements.
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1 Yoojin Jeong, Yoojin Jeong, et al, Abstract 5406: Evaluation of antitumor effects of plogosertib, PLK1 inhibitor in biliary tract cancer with BUBR1 as a potential biomarker, Cancer Res (2025) 85 (8 Supplement 1): 5406. https://doi.org/10.1158/1538-7445.AM2025-5406.
