Abstract LB-211: Targeting triple negative breast cancer by using non-oncologic drug targets.

Abstract Background: Triple negative breast cancer (TNBC) is defined by the lack of estrogen-receptor alpha (ERα) and pro-gesterone receptor (PGR) expression as well as absence of human epidermal growth factor receptor2 (HER2/neu) overexpression. This type of breast cancer is characterized by a poor prognosis and sig-nificantly reduced survival rate compared to other breast cancer subtypes. This is mostly due to the lack of targeted agents like endocrine or anti HER2 targets. Gene expression analysis revealed that different molecular targets are overexpressed in triple nega-tive breast cancer compared to other breast cancer subtypes. Therefore, these drug targets hold great potential for newly personalized therapeutic approaches in TNBC as well as other cancer types. Methods: Based on a list previously published (Liedtke et al., Cancer Res 2009) we defined the enzyme ALOX5 (arachidonate 5-lipoxygenase) as being a prominent new potential drug target. By using a set of known inhibitors of ALOX5 we deeply analyzed the effect on triple negative breast cancer cells as well as other breast cancer subtypes. Results: We firstly could show, that expression of ALOX5 correlates with the subtype of triple negative breast cancer, by trend. Treatment with meclofenamic acid additionally, showed significant decrease of proliferative capacity in at least some triple negative breast cancer cell lines. Conclusion: We could show that - in case of ALOX5 - its expression correlates with the triple negative breast cancer subtype by trend. Therefore, an inhibition of this molecular target might provoke anti prolife-rative effects on triple negative breast cancer cells. Actually, treatment with meclofenamic acid - a drug already used for joint, arthritis, muscular pain - showed reduction of proliferation in triplen negative breast cancer cells. Whether this effect relies on inhibition of ALOX5 or its function has to be analyzed further. Citation Format: Christof Bernemann, Carolin Huelsewig, Marie-Kristin von Wahlde, Ludwig Kiesel, Cornelia Liedtke. Targeting triple negative breast cancer by using non-oncologic drug targets. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-211. doi:10.1158/1538-7445.AM2013-LB-211