Recently, many preclinical and clinical researches have focused on the possible roles of new therapeutic modalities to enhance current treatment efficacy or to extend the current limitations against breast cancer treatment. Th melanoma differentiation-associated gene-7 (mda-7 ), now classified as a member of the interleukin (IL)-10 gene family, has attracted attentions from several investigators for its unique ability to act against various cancers including breast cancer. In addition to mda-7, highly selective cyclooxygenase-2 (Cox-2) inhibitors, have continuously demonstrated possible anticancer effects against various cancers even though theray with many of the inhibitors has resulted in major set backs due to complications after long-term use. However, few have performed to demonstrate the synergistic effects of these two efficient treatment options or to demonstrate preventive measures to reduce the size of tumors. We summarize important results and our experience related to the use of a selective cyclooxygenase 2 inhibitor and adenovirus-mediated delivery of mda-7.