A breast cancer-specific combinational QSAR model development using machine learning and deep learning approaches

Breast cancer is the most prevalent and heterogeneous form of cancer affecting women worldwide. Various therapeutic strategies are in practice based on the extent of disease spread, such as surgery, chemotherapy, radiotherapy, and immunotherapy. Combinational therapy is another strategy that has proven to be effective in controlling cancer progression. Administration of Anchor drug, a well-established primary therapeutic agent with known efficacy for specific targets, with Library drug, a supplementary drug to enhance the efficacy of anchor drugs and broaden the therapeutic approach. Our work focused on harnessing regression-based Machine learning (ML) and deep learning (DL) algorithms to develop a structure-activity relationship between the molecular descriptors of drug pairs and their combined biological activity through a QSAR (Quantitative structure-activity relationship) model. 11 popularly known machine learning and deep learning algorithms were used to develop QSAR models. A total of 52 breast cancer cell lines, 25 anchor drugs, and 51 library drugs were considered in developing the QSAR model. It was observed that Deep Neural Networks (DNNs) achieved an impressive R² (Coefficient of Determination) of 0.94, with an RMSE (Root Mean Square Error) value of 0.255, making it the most effective algorithm for developing a structure-activity relationship with strong generalization capabilities. In conclusion, applying combinational therapy alongside ML and DL techniques represents a promising approach to combating breast cancer.