A pan-cancer, pan-treatment model for predicting drug responses from patient-derived xenografts

The translatability of patient-derived xenograft (PDX)-generated clinical data into patient-specific outcomes for therapeutic guidance is limited by the challenges in generalizability of models across patients, treatments, and cancer types. Previously, machine learning (ML) models have been developed for the two most abundant cancer types, i.e. breast cancer and colorectal cancer, but these are unusable in other cancer types because each treatment/cancer type requires a different model to be trained. Here, we provide an ML framework to train a single pan-cancer, pan-treatment model for predicting treatment outcomes. We show that such models give promising results for all cancer types considered and reproduce the accuracy levels of individually trained cancer types. In the proposed model, all PDX genomic profiles from all cancer types are used as the training data, and instead of partitioning them into cancer types for each model, the cancer type and treatment name are appended as the input features of the training model. Using genomic-only and treatment-only embeddings and combining them with principal component analysis-based dimensionality reduction, our models show promising results and provide a framework for further improvements and real-time use for best treatment selections for cancer patients.