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Oncotarget. 2017 Apr 18;8(16):26066-26078. doi: 10.18632/oncotarget.15257.

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

Author information

1
Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
2
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.
3
Pharmaxis Pharmaceutical Ltd., Frenchs Forest, Australia.

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.

KEYWORDS:

breast cancer; lysyl oxidase; lysyl oxidase-like 2; metastasis

PMID:
28199967
PMCID:
PMC5432238
DOI:
10.18632/oncotarget.15257
[Indexed for MEDLINE]
Free PMC Article

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