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Breast cancer is the most diagnosed cancer in women in the United States, and despite improved prognosis resulting from targeted therapies, tumors commonly re-emerge upon development of therapeutic resistance. In order to overcome this, it is critical to explore the cellular pathways that change in tumors following treatment. While many mechanisms of resistance to targeted therapies have been identified, the metabolic changes that occur following treatment have not been well defined. We believe that these changes may offer a general therapeutic target. Using a doxycycline-inducible Her2 mouse model of breast cancer, we are exploring the molecular and cellular consequences Her2 inhibition. Using in vitro mammosphere cultures derived from these mice, we showed that Her2 loss quickly downregulates ERK and Akt signaling. There is a corresponding decrease in proliferation, and apoptosis is induced in 25-50% of cells. However, a population of cells survives Her2 withdrawal and remains dormant for upwards of one month. We are using these models to study how metabolic pathways are rewired following Her2 inhibition, and we believe that the metabolic pathways adapted upon Her2 inhibition may represent targetable vulnerabilities. Note: This abstract was not presented at the meeting. Citation Format: Douglas B. Fox, James V. Alvarez. Her2 inhibition and dormant cell metabolism [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 4947. doi:10.1158/1538-7445.AM2017-4947