Yang Jia-Sin, Lin Chiao-Wen, Su Shih-Chi, Yang Shun-Fa
a Department of Medical Research , Chung Shan Medical University Hospital , Taichung , Taiwan.
b Institute of Medicine , Chung Shan Medical University , Taichung , Taiwan.
Expert Opin Drug Metab Toxicol. 2016;12(2):191-200. doi: 10.1517/17425255.2016.1131820. Epub 2016 Jan 11.
Matrix metalloproteinases (MMPs) are classified in the family of zinc-dependent endopeptidases, which can degrade various components of an extracellular matrix and a basement membrane. Studies have demonstrated that MMPs relate to the development of malignant tumors and induce angiogenesis, resulting in the invasion and metastasis of tumor cells. MMPs are highly expressed in malignant tumors and are related to cancer patients' malignant phenotype and poor prognosis. Therefore, blocking the expression or activity of MMPs may be a promising strategy for cancer treatment.
This study aimed to explain the MMP structure, regulatory mechanism, and carcinogenic effect; investigate the matrix metalloproteinase-inhibitors (MMPIs) that are currently used in clinical trials for cancer treatment; and summarize the trial results.
Currently, the results of clinical trials that have used MMPIs as anticancer agents are unsatisfactory. However, MMPs remain an attractive target for cancer treatment. For example, development of the specific peptide or antibodies in targeting the hemopexin domain of MMP-2 may be a new therapeutic direction. The design and development of MMPIs that have selectivity will be the primary focus in future studies.
基质金属蛋白酶(MMPs)属于锌依赖性内肽酶家族,能够降解细胞外基质和基底膜的各种成分。研究表明,MMPs与恶性肿瘤的发展相关,并诱导血管生成,从而导致肿瘤细胞的侵袭和转移。MMPs在恶性肿瘤中高表达,与癌症患者的恶性表型和不良预后相关。因此,阻断MMPs的表达或活性可能是一种有前景的癌症治疗策略。
本研究旨在阐释MMP的结构、调控机制和致癌作用;研究目前用于癌症治疗临床试验的基质金属蛋白酶抑制剂(MMPIs);并总结试验结果。
目前,将MMPIs用作抗癌药物的临床试验结果并不理想。然而,MMPs仍然是癌症治疗的一个有吸引力的靶点。例如,开发靶向MMP-2血红素结合蛋白结构域的特异性肽或抗体可能是一个新的治疗方向。具有选择性的MMPIs的设计和开发将是未来研究的主要重点。