Abstract 1166: Inhibition of tumor growth in mouse models of cancer by systemic delivery of tumor suppressor miRNAs

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.1166-1166
• Main Authors: Brown, David, Daige, Chris, Wiggins, Jason, Kelnar, Kevin, Ruffino, Lynnsie, Omotola, Michael, Zhou, Jane, Bader, Andreas
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-1166

Tumor suppressor miRNAs represent an intriguing new class of biomolecules that might be developed into therapeutic candidates for cancer. Based upon its involvement in the p53 pathway and its capacity to regulate cell cycle and apoptosis via multiple oncogenic pathways, miR-34 might be the most intriguing of the tumor suppressor miRNAs. We have developed mimics of the miR-34 tumor suppressor that have been tested for efficacy using xenograft and transgenic mouse models of cancer. When complexed with an effective delivery agent, tail-vein injected miR-34 mimics have proven capable of inhibiting the growth and metastasis of mature tumors. When delivered systemically to BalbC mice, the same complexed miR-34 mimics fail to incease the serum levels of liver, kidney, and heart toxicity markers. Systemically delivered miR-34 mimics also failed to induce cytokines in mice. The development of miR-34 mimics with enhanced pharmacokinetic profiles and a systemic delivery formulation that can be manufactured under cGMP conditions are underway. Preclinical efficacy, PK/PD, and rodent safety data will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1166. doi:10.1158/1538-7445.AM2011-1166