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.
Highlights
Solid tumors remain one of the biggest burdens of disease in the developed world
The PXS compounds as a new generation of Lysyl Oxidase-like 2 (LOXL2) inhibitors β-aminopropionitrile (BAPN) has long served as the archetypal lysyl oxidase inhibitor, variable potency, and selectivity, has often been reported
We present the first data to show that selective targeting of LOXL2 using small molecule inhibitors is effective against primary breast tumor burden
Summary
Solid tumors remain one of the biggest burdens of disease in the developed world. Surgery remains the gold standard for treating patients with resectable disease. Early detection is seen as one of the most effective approaches for improving patient survival. There is mounting evidence that changes in the extracellular matrix (ECM) are critical in promoting the growth and metastatic dissemination of solid tumors[1]. Many of the biochemical and biomechanical changes in the tumor ECM are a direct result of tumor action [2]. Particular focus has been on the role of matrix remodeling enzymes, and their function in promoting tumor progression [3]. Enzymes that post-translationally modify the ECM, and in particular those that cross-link the ECM, such as the lysyl oxidase family are of particular interest as targetable molecules [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
