Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Faculty Publications Article Faculty Publications -Articles Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Banerjee, Dyuti; Krishnan, Sivaneasan Bala; Upreti, Kamal; Tharewal, Sumegh Shrikant; Shankar, Uma; Kshirsagar, Pravin; Kumar, Manoj Title A name given to the resource Data-Driven Drug Discovery Optimization for Breast Cancer Using Interpretable Machine Learning Models Date A point or period of time associated with an event in the lifecycle of the resource 01-01-2025 Source A related resource from which the described resource is derived Journal of Visualized Experiments;Volume;2025;Issue;223; Identifier An unambiguous reference to the resource within a given context <a href="https://doi.org/10.3791/68705" target="_blank" rel="noreferrer noopener">https://doi.org/10.3791/68705</a> <br /><br /><a href="https://www.scopus.com/pages/publications/105018502113?origin=resultslist" target="_blank" rel="noreferrer noopener">https://www.scopus.com/pages/publications/105018502113?origin=resultslist</a> Coverage The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant Banerjee D., Koneru Lakshmaiah Education Foundation, India; Krishnan S.B., Singapore Institute of Technology, Singapore; Upreti K., Christ University, India; Tharewal S.S., DBS Global University, India; Shankar U., Qaiwan International University, Iraq; Kshirsagar P., J D College of Engineering &amp; Management, India; Kumar M., Gurukula Kangri University, India Description An account of the resource Breast cancer remains one of the most prevalent malignancies worldwide, posing significant therapeutic challenges due to tumor heterogeneity and drug resistance. This study presents a reproducible, data-driven machine learning protocol for predicting drug sensitivity in breast cancer cell lines, with the dual objective of identifying potent single agents and synergistic drug combinations. Using curated datasets from the Genomics of Drug Sensitivity in Cancer (GDSC), two predictive approaches were implemented: a standalone XGBoost regressor and a hybrid Autoencoder-XGBoost pipeline. Preprocessing included label encoding, one-hot encoding, Z-score standardization, missing value imputation, and dimensionality reduction via PCA. Model evaluation demonstrated that XGBoost achieved superior performance (MSE = 1.3789, R2 = 0.8145) compared to the hybrid model (MSE = 4.0322, R2 = 0.4577). Interpretability was addressed using SHapley Additive exPlanations (SHAP), which identified TARGET_PATHWAY, DRUG_ID, TARGET, and CELL_LINE_NAME as key predictive features, aligning with established pharmacological mechanisms. Predicted synergy scores, derived from combining model outputs with DrugComb and SynergyDB data, highlighted promising drug pairs such as Bortezomib + Romidepsin and Paclitaxel + Bortezomib. These findings were further supported by PCA-based pharmacological clustering, revealing biologically relevant groupings of drugs with similar mechanisms of action. The proposed protocol provides a transparent and adaptable framework for precision oncology research, enabling both predictive accuracy and biological interpretability. By integrating rigorous preprocessing, model validation, explainability, and drug synergy analysis, this workflow offers a scalable foundation for translational drug discovery and repurposing in breast cancer treatment. 2025 JoVE Journal of Visualized Experiments. Publisher An entity responsible for making the resource available MyJoVE Corporation Relation A related resource ISSN: 1940087X; Language A language of the resource English Type The nature or genre of the resource Article Rights Information about rights held in and over the resource Restricted Access; Hardcopy may be available in the library Format The file format, physical medium, or dimensions of the resource online