Multifaceted Biological Spectra of Tandyukisin Against Breast Cancer: Targeting <scp>ERBB2</scp> Signaling and Beyond

ABSTRACT Breast cancer remains a leading cause of mortality among women aged 45–55, driven by factors such as hormonal imbalances, iodine deficiency, and aging. Significant side effects and collateral damage to healthy tissues limit the effectiveness of current treatments, such as surgery, chemotherapy, and radiation therapy. Tandyukisin, a marine‐derived compound, shows potential as a novel therapeutic agent targeting drug‐resistant EGFR and HER2 mutations. This study investigates the therapeutic potential of Tandyukisin against breast cancer through network pharmacology, molecular docking, and molecular dynamics simulations, focusing on its interactions with ERBB2 and associated signaling pathways. Potential breast cancer‐specific targets for Tandyukisin were identified through SwissTargetPrediction and GeneCards databases, with overlaps analyzed using Venny 2.1. Functional enrichment and protein–protein interaction analyses were conducted using STRING and Cytoscape version 3.10.3. Molecular docking was performed using AutoDock Vina to assess binding affinity with ERBB2, while molecular dynamics simulations evaluated the stability and conformational dynamics of Tandyukisin‐ERBB2 complexes. Tandyukisin targets 27 breast cancer‐relevant proteins, prominently ERBB2. Functional enrichment analysis revealed its role in apoptotic regulation and critical pathways like PI3K‐Akt and MAPK. In addition, molecular docking demonstrated strong binding affinity and stable interactions with ERBB2, and molecular dynamics simulations showed Tandyukisin‐ERBB2 complex atomic deviation and residual fluctuation, confirming enhanced stability. Additionally, pathway analysis identified Tandyukisin's disruption of EGFR resistance and VEGF signaling, emphasizing its multifactorial anti‐tumor effects. Tandyukisin exhibits promising therapeutic efficacy for breast cancer by selectively targeting ERBB2, modulating key signaling pathways, and minimizing off‐target effects. Its stability and specificity position it as a candidate for advanced breast cancer therapy, with the potential for addressing drug resistance and improving outcomes. Further experimental validation is required to substantiate these findings.