FUSED: Cross-Domain Integration of Foundation Models for Cancer Drug Response Prediction

AI-driven methods for predicting drug responses hold promise for advancing personalized cancer therapy, but cancer heterogeneity and the high cost of data generation pose substantial challenges. Here we explore the transfer learning capability and introduce FUSED ( Fu sion of Foundation Model E mbeddings for D rug Response Prediction), a novel architecture for cross-domain foundation model (FM) integration. By systematically benchmark FMs across two domains – molecular FM for drugs and single-cell FM for cell lines, we demonstrate that integrating single-cell FMs substantially reduces the number of input features required for cell line representation. Among FMs, Molformer significantly outperforms ChemBERTa, and scGPT surpasses scFoundation in predictive accuracy and training stability. Moreover, integrating single-cell FMs improves performance in both drug-known and leave-one-drug-out scenarios. These findings highlight the potential of cross-domain FM integration for more efficient and robust drug response prediction.