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

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

doi:10.18632/oncotarget.15257

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

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

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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.

Original language	English
Journal	OncoTarget
Volume	8
Issue number	16
Pages (from-to)	26066-26078
Number of pages	13
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.15257
Publication status	Published - 10 Feb 2017

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Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancerFinal published version, 12.8 MBLicence: CC BY

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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.",

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T1 - Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer

AU - Chang, Joan

AU - Lucas, Morghan C

AU - Leonte, Lidia Elena

AU - Garcia-Montolio, Marc

AU - Singh, Lukram Babloo

AU - Findlay, Alison D

AU - Deodhar, Mandar

AU - Foot, Jonathan S

AU - Jarolimek, Wolfgang

AU - Timpson, Paul

AU - Erler, Janine Terra

AU - Cox, Thomas Robert

PY - 2017/2/10

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N2 - 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.

AB - 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.

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DO - 10.18632/oncotarget.15257

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SP - 26066

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JF - Oncotarget

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

Abstract

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