Molecularly targeted therapies that inhibit the estrogen pathway or that target amplified Her2/Neu are efficacious in the treatment of breast cancer. Patients whose tumors do not express estrogen receptor (ER), progesterone receptor (PR), or amplified Her2/Neu, a subset comprising 20% of breast cancer patients, do not benefit from the validated targeted therapies (i.e., anti-estrogen therapies and Herceptin) and can only be treated with chemotherapy. These triple-negative tumors tend to present with poor prognostic features and the patients who express these tumors have a poor outcome compared to those whose tumors express ER, PR, and/or have amplified Her2/Neu. In a new initiative, we are using RNAi technology in a functional genomic approach to identify kinases that are therapeutic targets in triple-negative breast cancer cells. We have identified a list of kinases that, when downregulated, lead to death in the cancer cells. Ongoing work is characterizing these kinases further.