Budding Uninhibited by Benzimidazole 1 in pancreatic cancer: theoretical, mechanistic and bioinformatic insights

Abstract Pancreatic Cancer (PC) is a highly metastatic malignancy that has a dismal prognosis, with a five-year survival rate of 2–9%. Despite its devastating global impact, effective methods for early diagnosis and treatment remain limited. BUB1 (Budding Uninhibited by Benzimidazole 1) is a mitotic serine/threonine kinase that is a pivotal component of the spindle assembly checkpoint (SAC). It plays a central role in governing the accurate attachment of spindle microtubules to kinetochores, consequently ensuring genomic fidelity. Beyond its canonical role in cell cycle regulation, recent studies have associated its overexpression with decreased overall survival in many patients with solid tumors, including PC. However, the molecular mechanisms underlying its role in PC are still not well characterized. In this review, we explore the possibility of BUB1 promoting the aggressiveness of PC by upregulating oncogenic signalling pathways such as TGF-β, as well as causing treatment failure through chemoresistance. We also provide a basic bioinformatic proof of concept highlighting the overexpression and protein interactions of BUB1 in PC, and its consequent theranostic potential. Graphical abstract