Abstract 2938: Polo-like kinase 1: a potential therapeutic target for the management of patients with triple negative breast cancer

Breast cancers are composed of molecularly distinct subtypes with different clinical outcomes and responses to therapy. Our aim is to discover potential therapeutic targets for triple negative breast cancer (TNBC), a poor prognosis subgroup with no targeted therapy available yet. Gene expression profiling on a cohort of 160 breast cancers including 40 TNBC revealed that the polo-like kinase 1 (PLK1), a protein kinase, is specifically over-expressed in TNBC compared to the other breast cancer subtypes. High PLK1 expression was confirmed at a proteomic level by reverse phase protein array and tissue microarray. In TNBC cell lines grown as monolayers, RNAi-mediated PLK1 depletion or small compound (BI-2536)-mediated PLK1 inhibition induced an increase in phosphorylated H2AX, G2/M arrest and apoptosis, resulting in a decrease in cell viability. In addition, a soft-agar colony assay showed that PLK1 silencing impaired tumorigenicity of TNBC cell lines. With cells grown in extracellular matrix gels (Matrigel), BI-2536 induced apoptosis specifically in TNBC cancerous versus “normal” cell lines. The in vivo anti-tumor effect of BI-2536 was investigated in two TNBC xenografts derived from patient's biopsies. When administrated as a single agent, the PLK1 inhibitor significantly impaired the tumor growth. Most importantly, administration of BI-2536 in combination with adriamycin + cyclophosphamide chemotherapy led to 100% complete response (9/9 mice). Altogether, our observations point out that PLK1 may represent an attractive therapeutic target, in association with conventional chemotherapy, for the management of patients with TNBC. 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 2938. doi:1538-7445.AM2012-2938