The present disclosure is directed to methodologies or technologies for generating a predictor of a disease state (e.g. cancer-therapy efficacy status, cancer therapy progress, cancer prognosis, cancer diagnosis, therapy failure, relapse, recurrence, and the like) based on genomic and proteomic signatures, gene expression, and pathways & networks activation of endogenous human stem cell-associated retroviruses (SCAR). This disclosure is also directed to methods of targeting, designing, and using treatments for clinically intractable malignant tumors.