Po-208 human zebrafish xenografts as therapy sensors for breast cancer

R Mendes, J Ribeiro, MJ Brito, F Cardoso, R Fior, M Godinho Ferreira
2018 Poster Presentation: Tumour Biology   unpublished
Material and methods A genetically engineered nanocarrier based on human ferritin heavy chain (HFt) able to incorporate and deliver drugs was developed. These nanoparticles contain a short motif sequence (MP) cleavable by matrix metalloproteases between the HFt subunit and a masking sequence rich in proline (P), alanine (A) and serine (S): HFt-MP-PASE40. A topoisomerase I inhibitor was loaded into these nanocarriers (HFt-MP-PASE-Topo). Cell viability of different pancreatic cancer cell lines
more » ... evaluated in vitro. In vivo the therapeutic efficacy of HFt-MP-PASE-Topo was investigated on both a pancreatic cancer cell-line-derived xenograft and a patientderived pancreatic cancer xenograft (PDX). Results and discussions In vitro studies showed a potent cytotoxic activity of HFt-MP-PASE-Topo with an IC50 that ranges between 0,005 mM to 0,05 mM. In vivo studies further demonstrated the therapeutic efficacy of HFt-MP-PASE-Topo in pancreatic cancer-bearing mice and in PDX model. In vivo treatments exhibited a robust decrease in tumour growth furthermore the animal overall survival significantly increased in HFt-MP-PASE-Topo treated mice. Conclusion Altogether, our results indicate that HFt-MP-PASE-Topo may constitute a promising tool in anticancer therapeutics.
doi:10.1136/esmoopen-2018-eacr25.727 fatcat:mufvi4cam5e6zb5swpvg2nkxxe