Poster Presentation 26th Lorne Cancer Conference 2014

Development of a Novel Small RNA Based Cancer Therapy Targeting Angiogenesis. (#232)

Prue N Plummer 1 2 , Brittany Umer 2 , Vito Ferro 3 , Michael Sax 2 , Alex Swarbrick 4 , Vivek Mittal 5 , Albert S Mellick 1 2
  1. School of Medicine, Deakin University , Geelong Waurn Ponds Campus, VIC, Australia
  2. Host Response to Cancer Laboratory, Griffith University, Southport, QLD, Australia
  3. School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia , QLD, Australia
  4. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  5. Lung Cancer Centre, Weill Cornell Medical College, New York, United States

Tumour angiogenesis is an important process in the development, growth and spread of tumours. There are several anti-angiogenic therapies currently used for cancer treatment, however these only extend the life of patients for a limited period of time due to the development of adaptive resistance and serious side-effects. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) have been implicated as being essential in this process and important in the establishment of metastasis1 2 3 4 . Therefore, targeting these cells is critical to stopping tumour vasculature development and spread. In a previous study we have shown that the Inhibitor of DNA Binding 1 (ID1) proximal promoter can be used to silence genes in EPCs, thus resulting in decrease in EPC mobilization, tumour growth and angiogenesis2 . We have also demonstrated the vital role microRNAs, in particular, miR-10b in promoting bone marrow mediated tumour angiogenesis . In particular, we found using fluorescent in situ hybridization of human breast cancer biopsies, that miR-10b is localised to the vasculature of aggressive late stage invasive ductal carcinoma. Furthermore, we demonstrated that directed targeting of miR-10b to tumour vasculature using an anti-miRNA encapsulated in a RGD conjugated liposomes can significantly decrease tumour vascular development, growth and EPC mobilization1 . Recently, we have synthesized an EPC specific peptide and successfully conjugated this to liposomes. We are in the process of testing the ability of this peptide to direct nucleic acid therapy to EPCs in vivo. As this approach would direct the anti-miRNA therapy to EPCs, we believe this may lead to a novel anti-cancer therapy without problems associated with current therapies.

  1. Plummer PN, Freeman R, Taft R et al. MicroRNAs Regulate Tumor Angiogenesis Modulated by Endothelial Progenitor Cells. Cancer Res. 73:341-52, 2013.
  2. Mellick AS, Plummer PN, Nolan D, et al. Using Transcription Factor Id1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumour Angiogenesis and Growth. Cancer Res. 70:7273-82, 2010.
  3. Nolan DJ, Ciarrocchi A, Mellick AS, et al. Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumour neovascularization. Genes & Dev. 21:1546-58, 2007.
  4. Gao D, Nolan DJ, Mellick AS, et al. EPCs control the angiogenic switch in mouse lung metastasis. Science. 319:195-8, 2008.