Abstract A03: Novel polyisoprenylated small molecules as potential new therapies for triple negative breast cancer

Abstract

Abstract Breast cancer patients whose tumors do not overexpress estrogen, progesterone or HER2 receptors do not benefit from the effective therapies targeting these receptors. Knowing what drives the tumors in the latter group of patients, known as triple negative breast cancer (TNBC), is important for developing more effective and less toxic therapies directed at these drivers. We have developed a novel class of compounds, the polyisoprenylated cysteinyl amide inhibitors (PCAIs) that target the aberrant growth signaling by EGFR and/or constitutively active mutant K-Ras in a significant proportion of TNBC and other aggressive cancers such as of the pancreas, colon and lungs. The PCAIs induced apoptotic cell death with EC50 values ranging from 2.2 to 2.7 µM. The PCAIs induced apoptosis in MDA-MB-231 spheroids as well as inhibited the spheroid formation at 1 and 2 µM, respectively. The PCAIs, at 1 µM, inhibited over 80% colony formation in MDA-MB-231 cells. At 1 and 2 µM, MDA-MB-231 Transwell cell invasion was inhibited by 80 and 94%, respectively. The PCAIs blocked tube formation in cultured HUVEC cells at 0.2 to 0.5 µM and vessel formation in chick embryos at 0.12 µg/egg. The PCAIs can thus be used as targeted therapies to inhibit tumor growth, cell migration and angiogenesis in TNBC and other cancers with excessive growth factors receptor and mutant K-Ras signaling. Citation Format: Olufisayo O. Salako, Augustine T. Nkembo, Elizabeth Ntantie, Nazarius S. Lamango. Novel polyisoprenylated small molecules as potential new therapies for triple negative breast cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A03.