Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer.
Pre-clinical evaluation of small molecule LOXL2 inhibitors in breast cancer.
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DOI：
10.18632/oncotarget.15257
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发表时间：
2017-04-18
期刊：
影响因子：
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通讯作者：
Cox TR
中科院分区：
文献类型：
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作者：
Chang J;Lucas MC;Leonte LE;Garcia-Montolio M;Singh LB;Findlay AD;Deodhar M;Foot JS;Jarolimek W;Timpson P;Erler JT;Cox TR
赖氨酰氧化酶样 2 (LOXL2) 是胺氧化酶赖氨酰氧化酶家族的成员，已知在正常组织发育和稳态以及实体瘤的发生和进展中发挥重要作用。在这里，我们在 MDA-MB-231 人类乳腺癌模型中测试了两代新型小分子 LOXL2 抑制剂的抗肿瘤特性。我们证实了 LOXL2 活性在原发性乳腺癌进展中的功能作用。抑制LOXL2活性可抑制原发肿瘤的生长并减少原发肿瘤血管生成。 LOXL2 和 LOX 的双重抑制显示出更大的效果，并且还导致肺和肝脏的总体转移负担降低。我们的数据提供了第一个证据来支持 LOXL2 特异性小分子抑制剂作为乳腺癌潜在疗法的作用。
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.