Tauro Marilena, Lynch Conor C
Department of Tumor Biology, H. Lee Moffitt Cancer Research Center and Institute, 12902 Magnolia Dr., Tampa, FL 33612, USA.
Cancers (Basel). 2018 Jun 5;10(6):185. doi: 10.3390/cancers10060185.
Bone metastatic breast cancer is currently incurable and will be evident in more than 70% of patients that succumb to the disease. Understanding the factors that contribute to the progression and metastasis of breast cancer can reveal therapeutic opportunities. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes whose role in cancer has been widely documented. They are capable of contributing to every step of the metastatic cascade, but enthusiasm for the use of MMP inhibition as a therapeutic approach has been dampened by the disappointing results of clinical trials conducted more than 20 years ago. Since the trials, our knowledge of MMP biology has expanded greatly. Combined with advances in the selective targeting of individual MMPs and the specific delivery of therapeutics to the tumor microenvironment, we may be on the verge of finally realizing the promise of MMP inhibition as a treatment strategy. Here, as a case in point, we focus specifically on MMP-2 as an example to show how it can contribute to each stage of breast-cancer-to-bone metastasis and also discuss novel approaches for the selective targeting of MMP-2 in the setting of the bone-cancer microenvironment.
骨转移性乳腺癌目前无法治愈，并且在超过70%死于该疾病的患者中会出现。了解促成乳腺癌进展和转移的因素能够揭示治疗机会。基质金属蛋白酶（MMPs）是一类蛋白水解酶，其在癌症中的作用已有广泛记载。它们能够促成转移级联反应的每一步，但20多年前进行的临床试验结果令人失望，这打击了将MMP抑制作为一种治疗方法的热情。自那些试验以来，我们对MMP生物学的认识有了极大扩展。结合在单个MMP的选择性靶向以及将治疗药物特异性递送至肿瘤微环境方面取得的进展，我们或许即将最终实现MMP抑制作为一种治疗策略的前景。在此，作为一个例证，我们特别聚焦于MMP-2，以展示它如何促成乳腺癌向骨转移的各个阶段，并且还讨论在骨癌微环境中选择性靶向MMP-2的新方法。
