Abstract B05: Repurposing FDA-approved drugs for anti-metastatic therapy: Results of an integrated genome wide screen for metastasis modifiers

Abstract

Abstract Metastasis remains the primary cause of patient morbidity and mortality in solid tumors. Recent advances in genomic technologies have provided major insights into the etiology of tumors. However, significantly less is known about factors that contribute to metastasis. Here we report the results of a genome-wide integrated genetic, transcriptional, and epigenetic analysis in a mouse mammary tumor model to identify factors associated with tumor progression. This strategy identified a prognostic transcription signature and several upstream transcriptional regulators for metastatic disease. Interestingly, this analysis also identified novel or other FDA-approved drugs as potentially useful for anti-metastatic therapy. As predicted by this screen, administration of antidiabetic thiazolidones Rosiglitazone and Pioglitazone suppressed metastasis in an orthotopic breast cancer mouse model. Similarly, ciprofloxacin, an antibiotic, also decreased breast cancer metastasis. This strategy is thus not only of prognostic value but also presents the opportunity to rapidly repurpose drugs with proven safety and efficacy profiles for control and treatment of advanced neoplastic disease. Citation Format: Anjali Shukla, Kent W. Hunter. Repurposing FDA-approved drugs for anti-metastatic therapy: Results of an integrated genome wide screen for metastasis modifiers. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B05.