CYCLACEL PHARMACEUTICALS HIGHLIGHTS PUBLICATION OF PRECLINICAL DATA SHOWING THAT PLOGOSERTIB IS ACTIVE IN A HARD-TO-TREAT SUBTYPE OF LIVER CANCER
Cyclacel Pharmaceuticals (NASDAQ: CYCC) announced the publication of preclinical data demonstrating the effectiveness of their drug plogosertib in treating fibrolamellar hepatocellular carcinoma (FLC), a rare liver cancer affecting young people with no approved treatments.
The study, published in the journal Gut, revealed that FLC cells are highly sensitive to PLK1 inhibition by plogosertib. The research showed that the DNAJ-PKAc fusion oncoprotein, which drives FLC progression, interacts with PLK1 at the centrosome. Notably, plogosertib demonstrated significant reduction in FLC growth while sparing normal liver cells in both in vitro and in vivo models.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) ha annunciato la pubblicazione di dati preclinici che dimostrano l'efficacia del loro farmaco plogosertib nel trattamento del carcinoma epatocellulare fibrolamellare (FLC), un raro tumore al fegato che colpisce i giovani e per il quale non esistono terapie approvate.
Lo studio, pubblicato sulla rivista Gut, ha evidenziato che le cellule FLC sono altamente sensibili all'inibizione di PLK1 da parte di plogosertib. La ricerca ha mostrato che la proteina oncogenica di fusione DNAJ-PKAc, che guida la progressione del FLC, interagisce con PLK1 al centrosoma. In particolare, plogosertib ha dimostrato una significativa riduzione della crescita del FLC, risparmiando le cellule epatiche normali sia in modelli in vitro che in vivo.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) anunció la publicación de datos preclínicos que demuestran la efectividad de su medicamento plogosertib en el tratamiento del carcinoma hepatocelular fibrolamelar (FLC), un cáncer hepático raro que afecta a jóvenes y para el cual no existen tratamientos aprobados.
El estudio, publicado en la revista Gut, reveló que las células FLC son altamente sensibles a la inhibición de PLK1 por plogosertib. La investigación mostró que la proteína oncogénica de fusión DNAJ-PKAc, que impulsa la progresión del FLC, interactúa con PLK1 en el centrosoma. Notablemente, plogosertib demostró una reducción significativa del crecimiento del FLC mientras preservaba las células hepáticas normales en modelos tanto in vitro como in vivo.
Cyclacel Pharmaceuticals (NASDAQ: CYCC)는 희귀 간암인 섬유판상 간세포암(FLC) 치료에 있어 자사의 약물 플로고서티브(plogosertib)의 효과를 입증한 전임상 데이터를 발표했습니다. FLC는 젊은 층에 영향을 미치며 승인된 치료법이 없는 질환입니다.
학술지 Gut에 게재된 연구에 따르면, FLC 세포는 플로고서티브에 의한 PLK1 억제에 매우 민감한 것으로 나타났습니다. 연구는 FLC 진행을 주도하는 DNAJ-PKAc 융합 온코단백질이 중심체에서 PLK1과 상호작용한다는 사실을 밝혔습니다. 특히, 플로고서티브는 시험관 내(in vitro) 및 생체 내(in vivo) 모델 모두에서 정상 간세포는 보호하면서 FLC 성장 억제에 상당한 효과를 보였습니다.
Cyclacel Pharmaceuticals (NASDAQ : CYCC) a annoncé la publication de données précliniques démontrant l'efficacité de leur médicament plogosertib dans le traitement du carcinome hépatocellulaire fibrolamellaire (FLC), un cancer du foie rare touchant les jeunes et sans traitement approuvé.
L'étude, publiée dans la revue Gut, a révélé que les cellules FLC sont très sensibles à l'inhibition de PLK1 par plogosertib. La recherche a montré que la protéine oncoprotéine de fusion DNAJ-PKAc, qui favorise la progression du FLC, interagit avec PLK1 au niveau du centrosome. Notamment, plogosertib a démontré une réduction significative de la croissance du FLC tout en épargnant les cellules hépatiques normales, aussi bien dans des modèles in vitro qu'in vivo.
Cyclacel Pharmaceuticals (NASDAQ: CYCC) hat die Veröffentlichung präklinischer Daten bekannt gegeben, die die Wirksamkeit ihres Medikaments Plogosertib bei der Behandlung von fibrolamellärem hepatozellulärem Karzinom (FLC) belegen, einer seltenen Leberkrebserkrankung, die junge Menschen betrifft und für die keine zugelassenen Therapien existieren.
Die in der Fachzeitschrift Gut veröffentlichte Studie zeigte, dass FLC-Zellen hochsensibel gegenüber der PLK1-Hemmung durch Plogosertib sind. Die Forschung ergab, dass das DNAJ-PKAc Fusions-Onkoprotein, das das Fortschreiten von FLC vorantreibt, am Zentrosom mit PLK1 interagiert. Bemerkenswert ist, dass Plogosertib das Wachstum von FLC in vitro und in vivo signifikant reduzierte, während normale Leberzellen geschont wurden.
- Plogosertib showed significant efficacy in reducing FLC growth in preclinical models
- Drug demonstrated selective action, sparing normal liver cells
- Research validates the mechanism of action through PLK1 inhibition
- Potential treatment option for an unmet medical need in rare liver cancer
- Results are only preclinical, requiring further studies before potential approval
- Additional clinical trials needed to confirm efficacy in humans
- Fibrolamellar hepatocellular carcinoma (FLC) has no approved treatment and
occurs mostly in adolescents and young adults -
KUALA LUMPUR, Malaysia, July 07, 2025 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; “Cyclacel” or the “Company”), a biopharmaceutical company developing innovative cancer medicines, highlighted a publication from independent investigators titled, “DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma,” published online in the journal Gut, a leading, peer-reviewed medical journal focused on gastroenterology and hepatology.1 The authors of the study described in the publication reported that DNAJ-PKAc, a fusion oncoprotein known to drive FLC progression, makes the cancer sensitive to treatment with plogosertib.
The researchers found that PLK1 is essential for FLC cells making them highly sensitive to loss of PLK1. A direct interaction was found between DNAJ-PKAc fusions present in the centrosome and PLK1, thus promoting mitotic progression. Pharmacologic inhibitors of PLK1, such as plogosertib, significantly reduced FLC growth but spared normal liver cells in patient-derived in vitro and in vivo xenograft models and an orthotopic model of FLC. The article suggests that plogosertib should be further evaluated as a potential treatment for FLC in further preclinical and clinical studies.
About fibrolamellar carcinoma (FLC)
According to the Fibrolamellar Cancer Foundation (FCF), FLC is a rare cancer of the liver that mainly occurs in adolescents and young adults. The National Cancer Institute estimates annual US incidence at 0.02 per 100,000. When FLC tissues from patients are examined under a microscope, distinctive fibrous bands, or lamellae, are observed. As patients initially do not have symptoms, FLC is frequently discovered at later stages or after spreading to other parts of the body. It is often misdiagnosed as HCC, hepatocellular carcinoma, the more common form of liver cancer. However, FLC is different from HCC as it is found in a younger population with normal livers and no known risk factors, such as hepatitis. Five-year survival for FLC patients is poor at approximately
The protein kinase A (PKA) enzyme is a common driver of FLC in patients. In nearly all FLC cases an abnormal form, or chimaera, is found which results from the fusion of the DNAJB1 and PKAc genes. FCF funded research at Rockefeller University identified this unique gene fusion in 2014 located at chromosome 19. The fusion is associated with breaking up of the chromosome, following which chromosomal reassembly is flawed resulting in cancer growth. Finding a DNAJB1–PKAc fusion in patient biopsies is confirmatory of an FLC diagnosis.
FLC does not respond to chemotherapy. Although surgery can be a cure if the cancer has not spread, there is an urgent need for systemic therapies to treat non-resectable FLC.
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 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 Chan M, Zhu S, Nukaya M, et al, DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma, Gut Published Online. doi: 10.1136/gutjnl-2024-334274.
FAQ
What is the significance of Cyclacel's plogosertib study for liver cancer treatment?
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