


Core Insights - Cyclacel Pharmaceuticals is developing plogosertib, a PLK1 inhibitor, as a potential treatment for fibrolamellar hepatocellular carcinoma (FLC), a rare liver cancer with no approved therapies [1][2][5] Group 1: Disease Overview - FLC primarily affects adolescents and young adults, with an estimated annual incidence in the US of 0.02 per 100,000 [3] - The five-year survival rate for FLC patients is approximately 30%, and the disease is often misdiagnosed as hepatocellular carcinoma (HCC) [3] - FLC is characterized by the presence of a unique DNAJB1-PKAc gene fusion, which is a common driver of the disease [4] Group 2: Research Findings - A recent study published in the journal Gut indicates that the DNAJ-PKAc fusion oncoprotein increases sensitivity to PLK1 inhibitors like plogosertib in FLC cells [1][2] - PLK1 is essential for the growth of FLC cells, and its inhibition leads to significant reduction in FLC growth while sparing normal liver cells [2] - The study suggests further evaluation of plogosertib in preclinical and clinical studies for FLC treatment [2] Group 3: Drug Development - Plogosertib is a selective and potent PLK1 inhibitor that has shown efficacy in human tumor xenografts at non-toxic doses [7] - Initial Phase 1 clinical study data indicate that plogosertib is well tolerated with no dose-limiting toxicity observed [8] - Cyclacel's strategy includes developing plogosertib for various solid tumors and hematological malignancies, with a focus on cancers associated with DNAJ-PKAc fusions [10]