a Section of Translational Breast Cancer Research, Department of Breast Medical Oncology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
b Division of Medicinal Chemistry , The University of Texas at Austin, College of Pharmacy , Austin , TX , USA.
Expert Opin Ther Targets. 2017 Sep;21(9):849-859. doi: 10.1080/14728222.2017.1363183. Epub 2017 Aug 16.
There is an unmet need in triple-negative breast cancer (TNBC) patients for targeted therapies. Maternal embryonic leucine zipper kinase (MELK) is a promising target for inhibition based on the abundance of correlative and functional data supporting its role in various cancer types. Areas covered: This review endeavors to outline the role of MELK in cancer. Studies covering a range of biological functions including proliferation, apoptosis, cancer stem cell phenotypes, epithelial-to-mesenchymal transition, metastasis, and therapy resistance are discussed here in order to understand the potential of MELK as a clinically significant target for TNBC patients. Expert opinion: Targeting MELK may offer a novel therapeutic opportunity in TNBC and other cancers. Despite the abundance of correlative data, there is still much we do not know. There are a lack of potent, specific inhibitors against MELK, as well as an insufficient understanding of MELK's downstream substrates. Addressing these issues is the first step toward identifying a patient population that could benefit from MELK inhibition in combination with other therapies.
三阴性乳腺癌（TNBC）患者对靶向治疗存在未满足的需求。基于大量相关性和功能数据支持其在各种癌症类型中的作用，母系胚胎亮氨酸拉链激酶（MELK）是抑制的一个有前途的靶点。
本文旨在概述 MELK 在癌症中的作用。讨论了涵盖一系列生物学功能的研究，包括增殖、凋亡、癌症干细胞表型、上皮-间充质转化、转移和治疗耐药性，以了解 MELK 作为 TNBC 患者临床意义靶点的潜力。
针对 MELK 可能为 TNBC 和其他癌症提供新的治疗机会。尽管相关性数据丰富，但我们仍有许多未知。针对 MELK 的有效、特异性抑制剂缺乏，对 MELK 的下游底物也缺乏足够的了解。解决这些问题是确定可能受益于 MELK 抑制与其他治疗联合的患者人群的第一步。
