Pharmacovigilance of ACTN4-Targeted Therapies: Monitoring Safety in Translational Oncology

Abstract

ACTN4 (Alpha-actinin-4), a pivotal cytoskeletal regulator, has been implicated in promoting tumor invasion, metastasis, and therapy resistance, particularly in oral cancer and other epithelial malignancies. With the advent of ACTN4 inhibitors and combination regimens targeting pathways such as EGFR, ensuring drug safety has become increasingly complex, necessitating advanced pharmacovigilance strategies. This review aims to evaluate current safety surveillance approaches, including the integration of data from the FDA Adverse Event Reporting System (FAERS), electronic health records (EHRs), social media monitoring, and machine learning-based risk prediction models. Recent findings highlight a rise in adverse drug reactions (ADRs) notably dermatologic, hepatic, and cardiovascular events associated with ACTN4 and EGFR inhibitor therapies, underscoring the challenges in early detection and causal assessment. Furthermore, AI-driven pharmacovigilance shows promise in identifying subtle safety signals and predicting high-risk patient cohorts, enabling personalized interventions and regulatory decision-making. The review concludes with a call for fully integrated AI-enabled pharmacovigilance frameworks to streamline real-time ADR detection, facilitate cross-platform data synthesis, and support translational advances in ACTN4-targeted drug safety surveillance.