Abstract
Drug resistance is a major challenge in cancer and infectious diseases, requiring innovative solutions. Recent research suggests that bacteria and cancer cells reprogram their metabolism and manipulate their external metabolic environment to resist a diverse range of therapeutics. Emerging technologies, including single-cell and spatial omics profiling, CRISPR chemogenomics, machine learning, and metabolic network modeling, have revealed the metabolic complexities within bacterial biofilms, tuberculosis granulomas, and the tumor microenvironment. Here, we examine metabolic mechanisms that aid drug resistance across these different disease areas; this includes activation of antioxidant defenses, manipulation of the host immune response, and rewiring of energy metabolism. This analysis of shared metabolic factors across diseases may inspire repurposing of drugs, immunotherapies, and dietary interventions to overcome resistance.