ArticleFrontiers in pharmacology2026
Trastuzumab-TKI combination in HER2-Positive tumors: a FAERS-Based safety profile and multimodal analysis of Tanespimycin's role in enhancing targeting of the HSP90AA1-PI3K-Akt-mTOR axis.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: This study addresses the safety profiles and molecular mechanisms of trastuzumab monotherapy and its combination with lapatinib, neratinib, and tucatinib for treating HER2-positive tumors. Methods: The research integrates a multi-platform approach, including data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), network pharmacology, molecular docking, molecular dynamics simulations, and Results: Pharmacovigilance analysis revealed that trastuzumab monotherapy was associated with an elevated incidence of cardiac and tumor progression-related adverse events (AEs). Combination therapies showed longer adverse event latency periods. Network pharmacology identified HSP90AA1 as a pivotal therapeutic target, while molecular docking and 100-ns molecular dynamics simulations confirmed the stable binding of each drug to HSP90AA1. Conclusion: This study establishes a novel framework for drug safety evaluation and provides a theoretical rationale for optimizing therapeutic strategies in HER2-positive tumors. These findings highlight the potential advantages of combination therapies regarding AE latency and elucidate the critical role of HSP90AA1.
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