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

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Dokumenter

Joan Chang, Morghan C Lucas, Lidia Elena Leonte, Marc Garcia-Montolio, Lukram Babloo Singh, Alison D Findlay, Mandar Deodhar, Jonathan S Foot, Wolfgang Jarolimek, Paul Timpson, Janine Terra Erler, Thomas Robert Cox

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.

OriginalsprogEngelsk
TidsskriftOncoTarget
Vol/bind8
Udgave nummer16
Sider (fra-til)26066-26078
Antal sider13
ISSN1949-2553
DOI
StatusUdgivet - 10 feb. 2017

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