Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer
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Joan Chang1, Morghan C. Lucas2, Lidia E. Leonte1, Marc Garcia-Montolio1, Lukram Babloo Singh1, Alison D. Findlay3, Mandar Deodhar3, Jonathan S. Foot3, Wolfgang Jarolimek3, Paul Timpson2, Janine T. Erler1, Thomas R. Cox1,2
1Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark
2The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
3Pharmaxis Pharmaceutical Ltd., Frenchs Forest, Australia
Thomas R. Cox, email: [email protected]
Janine T. Erler, email: [email protected]
Keywords: lysyl oxidase-like 2, lysyl oxidase, breast cancer, metastasis
Received: August 26, 2016 Accepted: January 17, 2017 Published: February 10, 2017
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 tumors. Here we tested the anti-tumor 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 tumor 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.
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