Molecular Mechanisms of Epirubicin in Multiple Myeloma: Targeting CDC20 for Enhanced Chemosensitivity and Cell Cycle Arrest

Abstract

Background: Epirubicin is a widely used chemotherapeutic agent for multiple myeloma (MM), but its clinical efficacy remains limited due to the inability to identify the subgroup of patients most likely to benefit. Identifying reliable biomarkers that can predict chemosensitivity is crucial for developing personalized treatment strategies and improving therapeutic outcomes. This review aims to characterize the molecular mechanisms of epirubicin in MM cells, explore its tumor-suppressive effects, and highlight potential biomarkers for patient stratification. Materials and Methods: The review synthesizes findings from studies on epirubicin's half-maximal inhibitory concentration (IC50) in MM cell lines, gene expression alterations following treatment, and bioinformatic analysis of publicly available datasets. We focus on CDC20, a key cell-cycle regulator, and its role as a prognostic biomarker for treatment response. In vitro assays, gene expression profiling, and in vivo xenograft models are explored to assess the impact of epirubicin on cell-cycle progression and tumor growth. Results: Epirubicin treatment leads to significant changes in gene expression, with CDC20 being one of the most markedly downregulated genes. Transcriptome analysis reveals that CDC20 suppression is associated with G2/M arrest and reduced tumor proliferation. Bioinformatic analysis of clinical datasets demonstrates that high CDC20 expression correlates with poorer survival outcomes, including shorter overall survival (OS), event-free survival (EFS), and post-progression survival (PPS). Conclusion: Epirubicin induces anti-myeloma effects by downregulating CDC20 and promoting cell-cycle arrest in MM cells. CDC20 serves as a potential biomarker for identifying MM patients who are likely to benefit from epirubicin-based therapies. These findings provide insights into the molecular underpinnings of epirubicin's action and the potential for using CDC20 as a predictive marker in precision oncology for MM.