DDSBC: A Stacking Ensemble Classifier-Based Approach for Breast Cancer Drug-Pair Cell Synergy Prediction

Breast cancer (BC) ranks as a leading cause of mortality among women worldwide, with incidence rates continuing to rise. The quest for effective treatments has led to the adoption of drug combination therapy, aiming to enhance drug efficacy. However, identifying synergistic drug combinations remains a daunting challenge due to the myriad of potential drug pairs. Current research leverages machine learning (ML) and deep learning (DL) models for drug-pair synergy prediction and classification. Nevertheless, these models often underperform on specific cancer types, including BC, as they are trained on data spanning various cancers without any specialization. Here, we introduce a stacking ensemble classifier, the drug–drug synergy for breast cancer (DDSBC), tailored explicitly for BC drug-pair cell synergy classification. Unlike existing models that generalize across cancer types, DDSBC is exclusively developed for BC, offering a more focused approach. Our comparative analysis against classical ML methods as well as DL models developed for drug synergy prediction highlights DDSBC's superior performance across test and independent datasets on BC data. Despite certain metrics where other methods narrowly surpass DDSBC by 1–2%, DDSBC consistently emerges as the top-ranked model, showcasing significant differences in scoring metrics and robust performance in ablation studies. DDSBC's performance and practicality position it as a preferred choice or an adjunctive validation tool for identifying synergistic or antagonistic drug pairs in BC, providing valuable insights for treatment strategies.