CYCLACEL PHARMACEUTICALS HIGHLIGHTS PRECLINICAL DATA SHOWING THAT CANCER OF THE BILIARY TRACT IS SENSITIVE TO PLOGOSERTIB
Cyclacel Pharmaceuticals (NASDAQ: CYCC) highlighted promising preclinical data showing the effectiveness of their drug plogosertib in treating biliary tract cancer (BTC). The study, published in Cancer Research, demonstrated that BTC cell lines were sensitive to plogosertib both as a standalone treatment and in combination therapy.
The research revealed that plogosertib works by promoting mitotic checkpoint complex formation, leading to mitotic arrest and cancer cell death. Importantly, the study identified BUBR1 as a potential biomarker for treatment effectiveness, with high BUBR1-expressing cells showing increased sensitivity to the drug. The findings suggest that targeting PLK1 with plogosertib could be an effective strategy for BTC treatment, particularly when combined with ATR inhibitors.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) ha evidenziato dati preclinici promettenti che dimostrano l'efficacia del loro farmaco plogosertib nel trattamento del tumore delle vie biliari (BTC). Lo studio, pubblicato su Cancer Research, ha mostrato che le linee cellulari di BTC sono sensibili al plogosertib sia come trattamento singolo che in terapia combinata.
La ricerca ha rivelato che il plogosertib agisce favorendo la formazione del complesso di checkpoint mitotico, causando l'arresto mitotico e la morte delle cellule tumorali. Importante, lo studio ha identificato BUBR1 come potenziale biomarcatore per l'efficacia del trattamento, con cellule ad alta espressione di BUBR1 che mostrano una maggiore sensibilit脿 al farmaco. I risultati suggeriscono che mirare a PLK1 con il plogosertib potrebbe rappresentare una strategia efficace per il trattamento del BTC, soprattutto se combinato con inibitori di ATR.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) destac贸 datos precl铆nicos prometedores que muestran la efectividad de su f谩rmaco plogosertib en el tratamiento del c谩ncer de las v铆as biliares (BTC). El estudio, publicado en Cancer Research, demostr贸 que las l铆neas celulares de BTC son sensibles al plogosertib tanto como tratamiento individual como en terapia combinada.
La investigaci贸n revel贸 que el plogosertib act煤a promoviendo la formaci贸n del complejo de control mit贸tico, lo que conduce a la detenci贸n mit贸tica y la muerte de las c茅lulas cancerosas. Es importante se帽alar que el estudio identific贸 a BUBR1 como un posible biomarcador para la efectividad del tratamiento, con c茅lulas que expresan altos niveles de BUBR1 mostrando una mayor sensibilidad al f谩rmaco. Los hallazgos sugieren que dirigir PLK1 con plogosertib podr铆a ser una estrategia eficaz para el tratamiento del BTC, especialmente cuando se combina con inhibidores de ATR.
Cyclacel Pharmaceuticals (NASDAQ: CYCC)電� 雼搓磤鞎�(BTC) 旃橂鞐� 鞛堨柎 鞎诫 顶岆瓿犾劀韹半笇(辫濒辞驳辞蝉别谤迟颈产)鞚� 須臣毳� 氤挫棳欤茧姅 鞙犽頃� 鞝勳瀯靸� 雿办澊韯半ゼ 氚滍憸頄堨姷雼堧嫟. Cancer Research 鞝�雱愳棎 瓴岇灛霅� 鞐瓣惮鞐愳劀 BTC 靹疙彫欤缄皜 雼弲 旃橂 氚� 氤戩毄 鞖旊矔 氇憪鞐愳劀 頂岆瓿犾劀韹半笇鞐� 氙缄皭頃潉 鞛呾頄堨姷雼堧嫟.
鞐瓣惮 瓴瓣臣鞐� 霐半ゴ氅�, 頂岆瓿犾劀韹半笇電� 鞙犾偓攵勳棿 鞝愱瞼 氤淀暕觳� 順曥劚鞚� 齑夓頃橃棳 鞙犾偓攵勳棿 鞝曥 氚� 鞎旍劯韽� 靷└鞚� 鞙犽弰頃╇媹雼�. 韸鬼瀳, 氤� 鞐瓣惮電� BUBR1鞚� 旃橂 須臣鞚� 鞛犾灛鞝� 氚旍澊鞓る旎る 頇曥澑頄堨溂氅�, BUBR1 氚滍槃鞚� 雴掛潃 靹疙彫臧� 鞎诫鞐� 雿� 氙缄皭頃� 瓴冹溂搿� 雮橅儉雮姷雼堧嫟. 鞚� 瓴瓣臣電� PLK1鞚� 響滌爜鞙茧 頃橂姅 頂岆瓿犾劀韹半笇臧� 韸鬼瀳 ATR 鞏奠牅鞝滌檧 氤戩毄 鞁� BTC 旃橂鞐� 須臣鞝侅澑 鞝勲灥鞚� 霅� 靾� 鞛堨潓鞚� 鞁滌偓頃╇媹雼�.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) a mis en avant des donn茅es pr茅cliniques prometteuses d茅montrant l'efficacit茅 de leur m茅dicament plogosertib dans le traitement du cancer des voies biliaires (BTC). L'茅tude, publi茅e dans Cancer Research, a montr茅 que les lign茅es cellulaires BTC 茅taient sensibles au plogosertib, tant en traitement seul qu'en th茅rapie combin茅e.
La recherche a r茅v茅l茅 que le plogosertib agit en favorisant la formation du complexe de contr么le mitotique, entra卯nant un arr锚t mitotique et la mort des cellules canc茅reuses. De mani猫re importante, l'茅tude a identifi茅 BUBR1 comme un biomarqueur potentiel de l'efficacit茅 du traitement, les cellules exprimant fortement BUBR1 montrant une sensibilit茅 accrue au m茅dicament. Ces r茅sultats sugg猫rent que cibler PLK1 avec le plogosertib pourrait 锚tre une strat茅gie efficace pour le traitement du BTC, notamment en association avec des inhibiteurs d'ATR.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) pr盲sentierte vielversprechende pr盲klinische Daten, die die Wirksamkeit ihres Medikaments plogosertib bei der Behandlung von Gallengangskarzinomen (BTC) zeigen. Die Studie, ver枚ffentlicht in Cancer Research, zeigte, dass BTC-Zelllinien sowohl als Monotherapie als auch in Kombinationstherapie empfindlich auf plogosertib reagieren.
Die Forschung ergab, dass plogosertib durch F枚rderung der Bildung des mitotischen Kontrollkomplexes wirkt, was zu einem Mitosearrest und dem Tod von Krebszellen f眉hrt. Wichtig ist, dass die Studie BUBR1 als potenziellen Biomarker f眉r die Behandlungseffektivit盲t identifizierte, wobei Zellen mit hoher BUBR1-Expression eine erh枚hte Empfindlichkeit gegen眉ber dem Medikament zeigten. Die Ergebnisse deuten darauf hin, dass die gezielte Hemmung von PLK1 mit plogosertib eine wirksame Strategie zur Behandlung von BTC sein k枚nnte, insbesondere in Kombination mit ATR-Inhibitoren.
- Preclinical data shows effectiveness of plogosertib in treating biliary tract cancer
- Discovery of BUBR1 as potential biomarker to predict treatment effectiveness
- Demonstrated synergistic effects when combined with ATR inhibitor
- Results are only preclinical and require further clinical validation
- Treatment effectiveness may be limited to patients with high BUBR1 expression
听听听听听听听听 - 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, 鈥�鈥� 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鈥檚 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鈥檚 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鈥�
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鈥檚 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聽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.听Cyclacel's聽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聽.听
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 鈥渕ay,鈥� 鈥渃ould,鈥� 鈥渨ill,鈥� 鈥渆xpects,鈥� 鈥渁nticipates,鈥� 鈥渁ims,鈥� 鈥渇uture,鈥� 鈥渋ntends,鈥� 鈥減lans,鈥� 鈥渂elieves,鈥� 鈥渆stimates,鈥� 鈥渢argets,鈥� 鈥渓ikely to鈥�, 鈥渦nderstands鈥� and similar statements. These forward-looking statements are based on management鈥檚 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鈥檚 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鈥檚 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 鈥淩isk Factors鈥� 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聽, or on the SEC Filings section of our Investor Relations website at聽. 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鈥檚 estimates as of the date of this press release. These forward-looking statements should not be relied upon as representing Cyclacel鈥檚 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聽(2025) 85 (8 Supplement 1): 5406. .
FAQ
What did Cyclacel Pharmaceuticals (CYCC) reveal about plogosertib's effectiveness in biliary tract cancer?
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What combination therapy showed promise with plogosertib in BTC treatment?
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