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Autotaxin and Breast Cancer: Towards Overcoming Treatment Barriers and Sequelae

机译:Autotaxin和乳腺癌:克服治疗障碍和后遗症。

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摘要

After a decade of intense preclinical investigations, the first in-class autotaxin inhibitor, GLPG1690, has entered Phase III clinical trials for idiopathic pulmonary fibrosis. In the intervening time, a deeper understanding of the role of the autotaxin–lysophosphatidate (LPA)–lipid phosphate phosphatase axis in breast cancer progression and treatment resistance has emerged. Concordantly, appreciation of the tumor microenvironment and chronic inflammation in cancer biology has matured. The role of LPA as a central mediator behind these concepts has been exemplified within the breast cancer field. In this review, we will summarize current challenges in breast cancer therapy and delineate how blocking LPA signaling could provide novel adjuvant therapeutic options for overcoming therapy resistance and adverse side effects, including radiation-induced fibrosis. The advent of autotaxin inhibitors in clinical practice could herald their applications as adjuvant therapies to improve the therapeutic indexes of existing treatments for breast and other cancers.
机译:经过十多年的深入临床前研究,第一个同类的自分泌运动抑制剂GLPG1690已进入特发性肺纤维化的III期临床试验。在此期间,人们逐渐认识到了自分泌紫杉醇-溶血磷脂酸(LPA)-脂质磷酸磷酸酶轴在乳腺癌进展和治疗抵抗中的作用。相应地,在肿瘤生物学中对肿瘤微环境和慢性炎症的认识已经成熟。 LPA作为这些概念背后的中心介体的作用已在乳腺癌领域得到了例证。在这篇综述中,我们将总结当前在乳腺癌治疗中的挑战,并描述阻断LPA信号传导如何为克服治疗耐药性和不良副作用(包括放射性纤维化)提供新的辅助治疗选择。自分泌抑制因子抑制剂在临床实践中的出现可预示其作为辅助疗法的应用,以改善现有的乳腺癌和其他癌症治疗方法的治疗指标。

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