Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer

• Published in: Oncotarget Vol. 8; no. 16; pp. 26066 - 26078
• Main Authors: Chang, Joan, Lucas, Morghan C, Leonte, Lidia E, Garcia-Montolio, Marc, Singh, Lukram Babloo, Findlay, Alison D, Deodhar, Mandar, Foot, Jonathan S, Jarolimek, Wolfgang, Timpson, Paul, Erler, Janine T, Cox, Thomas R
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 18.04.2017
• Subjects: Amino Acid Oxidoreductases - antagonists & inhibitors; Amino Acid Oxidoreductases - genetics; Aminopropionitrile - pharmacology; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer-Associated Fibroblasts - drug effects; Cancer-Associated Fibroblasts - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Enzyme Inhibitors - pharmacology; Female; Gene Knockdown Techniques; Gene Silencing; Humans; Mice; Neoplasm Metastasis; Neovascularization, Pathologic; Research Paper; Xenograft Model Antitumor Assays; lysyl oxidase-like 2; breast cancer; lysyl oxidase; metastasis
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15257

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.