Abstract 3366: An inhibitor of the NF-kappaB pathway targets cancer stem cells and prevents tumor recurrence

Abstract

Abstract Multidrug resistance and tumor recurrence are two of the major challenges in cancer treatment. Cancer stem cells (CSCs), found in most solid tumor types, have been proposed as the root cause of cancer growth and recurrence. These CSCs share similarities with normal Stem Cells, such as “stemness” gene profile expression, overexpression of Sox2, Nanog and Oct4, as well as ability to grow in spheres and to repopulate tumors. Additionally, CSCs also have a high resistance to chemotherapeutic agents, probably due to their dormancy and overexpression of ABC transporters. Since CSCs markers are highly variable between cell lines and tumor samples, we used a functional assay to select a drug candidate targeting CSCs, based on their capability to efflux dyes such as Hoechst 33324 by a side population (SP). This drug decreased SP and spheres formation in vitro, and reduced protein expression of CSC genes such as Sox2, Nanog, Survivin and Oct4. Another serious limitation of cancer chemotherapy is its toxic side effect due to poor targeting to the tumor and its microenvironment (TME). To address this issue, we developed targeted nanoparticles (tNP) to deliver chemotherapeutic drugs specifically to tumor cells and their TME, resulting in substantially reduced systemic toxicity, as well as eradication of tumors and prevention of their recurrence in a preclinical setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3366. doi:1538-7445.AM2012-3366