Abstract 3722: Quinacrine and sorafenib combination as potential therapy for anaplastic thyroid cancer

Abstract

Abstract Anaplastic thyroid cancer (ATC) is uncommon and represents 2-5% of all thyroid cancers. It remains amongst the most lethal human cancers with a reported median survival of 6 months despite therapy. ATC represents over 50% of all thyroid cancer fatalities annually. We have previously shown the effectiveness of quinacrine in combination with standard therapies in hepatocellular and colon carcinoma. Quinacrine has been used in the past to treat lupus and malaria and in addition to being available and affordable (∼30 USD/month of therapy) it has a well-known and acceptable toxicity profile. Here, we evaluate the efficacy of quinacrine in combination with sorafenib on a panel of human anaplastic thyroid cancer tumor cells. We observed that quinacrine as a single agent effectively kills anaplastic thyroid cancer cells in vitro in a concentration-dependent manner as assessed by CellTiter-Glo and sub-G1 analysis. Quinacrine in combination with sorafenib provides an additive effect in vitro. On analyzing, we observe that the anti-apoptotic Bcl-2 family member Mcl-1, which is over-expressed in a number of solid tumors is down-regulated with this combination treatment. Unlike chloroquine that inhibits autophagy, our previous results have not shown that quinacrine's anti-tumor efficacy involves alterations in autophagy. We are testing the quinacrine plus sorafenib combination in vivo by sub-cutaneous or orthotopic injection in immune-deficient mice of established cell lines as well as freshly isolated cells from patients with anaplastic thyroid cancer. Our findings suggest that quinacrine in combination with sorafenib may be an effective therapeutic strategy for anaplastic thyroid cancer. 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 3722. doi:1538-7445.AM2012-3722