Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer
Joan Chang1, Morghan C Lucas2, Lidia E Leonte1
1Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH), Copenhagen, Denmark.
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.
Insights
Novel small molecule inhibitors targeting Lysyl Oxidase-like 2 (LOXL2) show anti-tumor properties in breast cancer models. Dual inhibition of LOXL2 and LOX reduced tumor growth and metastasis, suggesting a potential new therapy.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Lysyl Oxidase-like 2 (LOXL2) is implicated in tissue development, homeostasis, and solid tumor progression.
- LOXL2 plays a role in the onset and advancement of various cancers.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of novel small molecule LOXL2 inhibitors.
- To investigate the role of LOXL2 in breast cancer progression and metastasis.
Main Methods:
- Utilized the MDA-MB-231 human breast cancer model.
- Tested two generations of small molecule LOXL2 inhibitors.
- Assessed tumor growth, angiogenesis, and metastatic burden.
Main Results:
- LOXL2 inhibition suppressed primary tumor growth and reduced angiogenesis.
- Dual inhibition of LOXL2 and LOX demonstrated enhanced anti-tumor effects.
- A significant reduction in lung and liver metastatic burden was observed with dual inhibition.
Conclusions:
- LOXL2 activity is functionally important in primary breast cancer progression.
- Small molecule LOXL2 inhibitors exhibit potential as a therapeutic strategy for breast cancer.
- Combined inhibition of LOXL2 and LOX may offer a more effective approach to managing breast cancer metastasis.
