title: Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer.
abstract: 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.
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
authors.forename: Joan
authors.initials: J
authors.lastname: Chang
authors.affiliation: The 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.
authors.forename: Morghan C
authors.initials: MC
authors.lastname: Lucas
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
authors.forename: Lidia E
authors.initials: LE
authors.lastname: Leonte
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
authors.forename: Marc
authors.initials: M
authors.lastname: Garcia-Montolio
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
authors.forename: Lukram Babloo
authors.initials: LB
authors.lastname: Singh
authors.affiliation: Pharmaxis Pharmaceutical Ltd., Frenchs Forest, Australia.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Findlay
authors.affiliation: Pharmaxis Pharmaceutical Ltd., Frenchs Forest, Australia.
authors.forename: Mandar
authors.initials: M
authors.lastname: Deodhar
authors.affiliation: Pharmaxis Pharmaceutical Ltd., Frenchs Forest, Australia.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Foot
authors.affiliation: Pharmaxis Pharmaceutical Ltd., Frenchs Forest, Australia.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jarolimek
authors.affiliation: The 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
authors.forename: Janine T
authors.initials: JT
authors.lastname: Erler
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.|The 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.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Cox
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000629:Aminopropionitrile; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human
keywords: breast cancer; lysyl oxidase; lysyl oxidase-like 2; metastasis