Cyclacel announces publication of preclinical data on plogosertib

Cyclacel Pharmaceuticals (CYCC) 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. 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.