Abstract 1774: The effects of diarylthiourea analogs on triple negative breast cancer cell growth

Abstract Breast cancer is the most common cancer occurring in women and the second leading cause of cancer death in women after lung cancer. Breast cancer is often classified at the molecular level in terms of whether the cancer expresses the estrogen receptor, progesterone receptor and human epidermal growth factor 2 receptor. Hormone receptor positive breast cancer accounts for 75-80% of all breast cancer and the remaining 20-25% accounts for the most aggressive types of cancer which are negative for all three receptors– known as triple negative breast cancer (TNBC). The current treatment used to manage TNBC is chemotherapy. Although chemotherapy has been effective in improving patients’ prognosis, a significant number of patients either relapse or develop resistance to these drugs. There is a significant interest in developing new therapeutic drugs aimed at improving outcomes in TNBC patients. Many studies have shown that flexible heteroarotinoids (Flex-Het) are a promising new class of drugs due to their ability to regulate growth, differentiation and apoptosis in a variety of cancer cells without activating the nuclear retinoic acid receptors. Previous studies have shown ShetA2 as the leading Flex-Het anti-cancer drug with the greatest efficacy in treating various types of cancer cells (Liu et al. 2004, Benbrook et al. 2005, and Liu et al. 2007). Some of the limitations of the ShetA2 are its high lipophilicity, toxic side effects and the low yields associated with the laborious synthesis. Therefore, efforts have been made to develop 2nd generation diarylthiourea compounds that retain anti-cancer activity, but with minimal side effects. The objective of this study was to examine the effects of two 2nd generation drugs SL1-18 and SL1-09 on various TNBC cell lines including MDA-MB-453, MDA-MB-231 and MDA-MB-468. Our preliminary data shows that exposure to micromolar levels of the diarylthiourea compounds effectively inhibited cancer cell growth in all three TNBC cell lines; however additional studies are necessary to understand the molecular mechanism of how SL1-18 and SL1-09 work to block cell growth and whether these anti-cancer drugs are promising therapeutic leads for the treatment of triple negative breast cancer. Citation Format: Deborah Nambi, Maggie C. Louie, Shengquan Liu. The effects of diarylthiourea analogs on triple negative breast cancer cell growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1774. doi:10.1158/1538-7445.AM2015-1774