Abstract
TPX2 is crucial for initiating microtubule formation from chromatin in human cells. It consists of two functional domains: The N-terminal fragment interacts with Aurora Kinase A (AURKA), while the C-terminal domain binds to microtubules. Elevated TPX2 levels have been identified as a predictive biomarker for enhanced malignancy in lung adenocarcinoma (LUAD). LUAD originates from the globular epithelial cells in the peripheral lung tissue and is often associated with smoking, although it is also common in non-smokers. The activity of AURKA, a critical serine/threonine kinase involved in mitosis, is mostly regulated by TPX2. Proper spindle assembly and chromosomal segregation during cell division depend on the activation of AURKA, which is facilitated by the connection between TPX2 and AURKA. To assess TPX2 dysregulation, we utilized transcriptomic servers, including GENT2, TIMER2.0, and GEPIA2, alongside cBioPortal for mutations and copy number variations. We examined the correlation between TPX2 expression and patient survival in LUAD using UALCAN and GEPIA2. Furthermore, in our investigation of potential therapeutic agents, we evaluated 500 marine-derived compounds through pharmacokinetics and toxicity analysis, human cytochrome P450 property assessment, molecular docking, and simulation. The MD over 200 ns indicated that marine compounds, such as Shellmycin C (CID:156581889) and Rhodoptilometrin (CID:625242), displayed significantly greater stability compared to the control drug Alisertib (CID:24771867). Consequently, these findings underscore the potential for developing innovative therapeutic strategies that target the AURKA-TPX2 complex in LUAD, warranting further validation through in vitro and in vivo studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00436-z.