Abstract 3899: Synthetic small molecule targeting CD24-/CD44+/ALDH+ cell population inhibits cancer stem cell activities in breast cancer

Abstract

Abstract Purpose of the study: Cancer stem cells (CSCs) have been described as the “seed of tumor”, and have been suggested as the driving force of tumor relapses. In this study we aimed to isolate small molecules via screening of the combinatorial chemical library. The isolated molecules bind CD24-/CD44+/ALDH+ breast cancer cell subpopulation with high selectivity and specificity. Experimental design and plan: Through the unbiased cell based chemical library screening, we identified compound candidates that specifically bind the stem-like cancer cell subpopulations in breast cancer cells and tissues. By performing in vitro, tissue and in vivo-based assessments on ligand-binding specificity and functional activities, we ensured that the isolated ligands target tumorigenic stem-like breast cell or tissue preferentially. Summary of discoveries and findings: The in vitro compound binding validations proved the specificity of the isolated compound candidates toward breast cancer cells and tissues displaying cancer stem cell properties. The compound-targeting cell populations display significantly-higher expressions of the well-known stem cell markers than the unbound cell populations. On the other hand, a series of biological and biochemical functional assays also confirmed the compound candidates exert tumor-suppression activities on breast cancer cell lines, such as slow down proliferation and reduce cell viability. More importantly, our study demonstrated that both isolated compounds have preferential selectivity and higher binding affinity to the TNBC cells and tissues, which have been reported for higher percentage of stem-like cancer cell population detected than in non-TNBC cells or tissues. Through mouse xenograft study followed by histological analysis, we further confirmed the binding specificity of the compound towards cell line models could be retained in vivo in mouse xenograft model. Conclusion: We demonstrated our ligand screening technique is able to identify synthetic compounds targeting cell subgroups or sub-populations of defined interest within one particular type of tumor. High specificity of the isolated molecules could be utilized to develop chemical probes for quantification of percentage of CSC in the tumor, which facilitates clinical evaluation of tumor relapse risk. The screening strategy also provides a new methodology in discovering novel drug targeting CSC subpopulations, not only in breast tumor, but also other types of human cancers. Funding: This project is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) grant, award ID: RP150713. Citation Format: Luxi Chen, Chao Long, Kha A. Tran, Jiyong Lee. Synthetic small molecule targeting CD24-/CD44+/ALDH+ cell population inhibits cancer stem cell activities in breast cancer [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 3899. doi:10.1158/1538-7445.AM2017-3899