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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.

Type Journal
ISBN 1949-2553 (Electronic) 1949-2553 (Linking)
Authors Chang, J.; Lucas, M. C.; Leonte, L. E.; Garcia-Montolio, M.; Singh, L. B.; Findlay, A. D.; Deodhar, M.; Foot, J. S.; Jarolimek, W.; Timpson, P.; Erler, J. T.; Cox, T. R.
Responsible Garvan Author Dr Thomas Cox
Publisher Name Oncotarget
Published Date 2017-04-18
Published Volume 8
Published Issue 16
Published Pages 26066-26078
Status Published in-print
DOI 10.18632/oncotarget.15257
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28199967