Poster Presentation 29th Lorne Cancer Conference 2017

Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer (#210)

Joan Chang 1 2 , Morghan C Lucas 3 , Lidia E Leonte 1 , Marc Garcia-Montolio 1 , Lukram Babloo Singh 1 , Alison D Findlay 4 , Mandar Deodhar 4 , Jonathan S Foot 4 , Wolfgang Jarolimek 4 , Paul Timpson 3 , Janine T Erler 1 , Thomas R Cox 1 3
  1. Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark
  2. Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
  3. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  4. Pharmaxis Pharmaceutical Ltd, Frenchs Forest, Australia

Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases is known to be important in normal tissue development and homeostasis, as well as the onset and progression of solid tumours. Here we tested the anti-tumour properties of two generations of novel small molecule LOXL2 inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumour angiogenesis. Dual inhibition of LOXL2 and LOX showed a greater effect and also led to a lower overall metastatic burden in the lung and liver. Our data provides the first evidence to support a role for LOXL2 specific small molecule inhibitors as a potential therapy in breast cancer.