Aurora kinase B at the nexus of cholesterol metabolism and therapy response in cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a heterogeneous and highly aggressive group of malignancies arising from the epithelial cells of the biliary tract. Although relatively uncommon, CCA has gained clinical relevance due to its steadily increasing global incidence and mortality. CCA now accounts for approximately 3% of gastrointestinal malignancies, ranking as the second most common hepatobiliary tumour. One of the most significant challenges in managing CCA lies in its typically asymptomatic presentation in early stages, leading to late diagnoses, when surgical resection, the only potentially curative option, is no longer viable.1 The prognosis for patients with CCA remains dismal, with 5-year survival rates below 20%.1 This poor outcome is compounded by the tumour’s genomic, epigenetic and molecular heterogeneity, which limits the efficacy of existing systemic therapies. In particular, the suboptimal performance of current chemotherapy and immunotherapy regimens highlights the urgent need for more effective treatment strategies. This therapeutic gap is largely attributable to an incomplete understanding of the molecular mechanisms driving CCA pathogenesis, underscoring the importance of elucidating its underlying biology to inform rational drug development. In light of the limited efficacy of current treatments, recent attention has shifted towards the role of metabolic reprogramming in tumour progression. In particular, accumulating evidence suggests that deregulated lipid metabolism is a common feature of cancer cells. Cholesterol is an essential component of cell membranes, modulating …