Abstract We earlier showed with Systems Biology approach that the genotoxic stress response evoked by cancer, infection, and radiation injury have similarities, particularly at the gastrointestinal tract. This was made possible using biophotonics, and show promise in drug screening opportunities using each of these pathologies as a surrogate model for one another. Using similar molecular Imaging methodology, we showed for the first time binding of osteoporosis drug bisphosphonate to prostate and ovarian cancer tumors and potential drug repurposing candidature. Recently, we presented similar drug re-tasking potential of 2-Deoxyglucose (2-DG) in anti-infection. Here, our data demonstrating mitigation of citrobacter rodentium infection by dietary treatment by 2-DG (0.4%), were analyzed with the bisphosphonate anti-infection response to enteric bacterial pathogens data reported elsewhere. Based on these results, a systems approach analysis is developed and presented demonstrating cross-talk and communication between different cells and integrated responses to pathogens and disease by 2-DG and bisphosphonate in anticancer and anti-infection actions. A role in EGFR signaling and modulation in the infiltration immune response cells by these two dissimilar compounds play a profound bridging event in anticancer and anti-infection activities. These system biology strategies will provide opportunities for drug repurposing in personalized cancer therapy and in anti-microbial management during cancer treatment. Also pave way for safer drugs in prevention and therapy of HER family-driven cancers. Citation Format: Rao V. Papineni, Shahid Umar, Alexey Goltsov, Ishfaq Ahmed. Deoxyglucose and bisphosphonate shows common pathways in its drug repurposed anticancer and anti-infection actions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-012. doi:10.1158/1538-7445.AM2017-LB-012