Matrix metalloproteinases as breast cancer drivers and therapeutic targets.
Matrix metalloproteinases as breast cancer drivers and therapeutic targets.
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DOI：
10.2741/4364
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发表时间：
2015-06-01
期刊：
影响因子：
--
通讯作者：
Radisky DC
中科院分区：
文献类型：
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作者：
Radisky ES;Radisky DC
基质金属蛋白酶（MMP）家族的成员已被鉴定为乳腺癌患者的不良预后标志物，并且在实验模型中作为肿瘤表型的许多方面的驱动因素。早期对MMPs作为治疗靶点的热情在使用广谱小分子催化位点抑制剂的令人失望的临床试验后有所缓和。然而，随后的研究继续定义MMP作为乳腺癌促进剂的关键作用，以阐明这些蛋白质在乳腺癌发展和进展中发挥的复杂作用，并确定这些作用如何与MMP家族单个成员的特定和独特的生化特征相关联。在这里，我们提供了一个概述的MMPs的结构特征，然后讨论临床研究确定哪些MMP家族成员与乳腺癌的发展和新的实验研究，揭示了这些特定的MMPs如何在乳腺癌微环境中发挥独特的作用。最后，我们讨论了最有前途的途径，能够针对肿瘤促进性能的基质金属蛋白酶的治疗药物的发展。
Members of the matrix metalloproteinase (MMP) family have been identified as poor prognosis markers for breast cancer patients and as drivers of many facets of the tumor phenotype in experimental models. Early enthusiasm for MMPs as therapeutic targets was tempered following disappointing clinical trials that utilized broad spectrum, small molecule catalytic site inhibitors. However, subsequent research has continued to define key roles for MMPs as breast cancer promoters, to elucidate the complex roles that that these proteins play in breast cancer development and progression, and to identify how these roles are linked to specific and unique biochemical features of individual members of the MMP family. Here, we provide an overview of the structural features of the MMPs, then discuss clinical studies identifying which MMP family members are linked with breast cancer development and new experimental studies that reveal how these specific MMPs may play unique roles in the breast cancer microenvironment. We conclude with a discussion of the most promising avenues for development of therapeutic agents capable of targeting the tumor-promoting properties of MMPs.