Abstract TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid), is an orally bioavailable synthetic retinoid, binding to nuclear retinoic acid receptor (RAR), activates selectively RAR alpha transcriptional. And TAC-101 has demonstrated anti-tumor activity and proplongation of survival in primary and metastatic liver cancer pre-clinical models. In Phase I study, the lymph nodes of a non-small cell lung cancer patient with nodal metastasis returned to normal size, constituting a complete radiologic response. In a Phase I/II trial of TAC-101 in patients with advanced hepatocellular carcinoma, TAC-101 showed significant disease stabilization, 2 PRs after discontinuing TAC-101 treatment, and prolonged median survival, suggesting that TAC-101 provides meaningful patient'ss benefit. Recently, many researchers have reported correlation between cancer stem-like cells and tumor malignancy, such as therapy-resistance. In addition, retinoids were reported to reduce the number of cells with the cancer stem cell marker. So, we hypothesize that TAC-101 induces the differentiation of cancer stem-like cells, and contributes life span prolongation of patients of solid tumor. We cultured A549 cancer cells in mediummedium containing 0.1 and 1 μM of TAC-101 for 8 weeks and analyzed the expression of several stem cell markers using flow cytomoetry technique. Detection method of side population was validated by the result that fumitremorgin C, inhibitor of ABCG2, could eliminate the side population. We found that TAC-101 reduced side-population, CD326 (EpCAM) positive population and standard deviation of side scatter. From these results, it is estimated that treatment of TAC-101 for a certain period of time will be enough to induce of differentiation and to reduce cancer stem-like cells, may result in the tumor shrinkage and prolongation of patient's survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3315.