Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL 33314, USA; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL 33314, USA; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Semin Cancer Biol. 2019 Jun;56:100-115. doi: 10.1016/j.semcancer.2017.11.008. Epub 2017 Nov 16.
Matrix metalloproteinases (MMPs) are members of zinc-dependent endopeptidases implicated in a variety of physiological and pathological processes. Over the decades, MMPs have been studied for their role in cancer progression, migration, and metastasis. As a result, accumulated evidence of MMPs incriminating role has made them an attractive therapeutic target. Early generations of broad-spectrum MMP inhibitors exhibited potent inhibitory activities, which subsequently led to clinical trials. Unexpectedly, these trials failed to meet the desired goals, mainly due to the lack of efficacy, poor oral bioavailability, and toxicity. In this review, we discuss the regulatory role of MMPs in cancer progression, current strategies in targeting MMPs for cancer treatment including prodrug design and tumor imaging, and therapeutic value of MMPs as biomarkers in breast, lung, and prostate cancers.
基质金属蛋白酶(MMPs)是锌依赖性内肽酶的成员,涉及多种生理和病理过程。几十年来,MMPs 一直被研究其在癌症进展、迁移和转移中的作用。因此,MMPs 参与作用的累积证据使它们成为一个有吸引力的治疗靶点。早期的广谱 MMP 抑制剂表现出很强的抑制活性,随后进行了临床试验。出乎意料的是,这些试验未能达到预期的目标,主要是由于缺乏疗效、口服生物利用度差和毒性。在这篇综述中,我们讨论了 MMPs 在癌症进展中的调节作用,目前靶向 MMPs 治疗癌症的策略,包括前药设计和肿瘤成像,以及 MMPs 作为乳腺癌、肺癌和前列腺癌生物标志物的治疗价值。