Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Eur J Pharmacol. 2024 Nov 5;982:176966. doi: 10.1016/j.ejphar.2024.176966. Epub 2024 Aug 30.
Cisplatin (CDDP) as one of the most common first-line chemotherapy drugs plays a vital role in the treatment of a wide range of malignant tumors. Nevertheless, CDDP resistance is observed as a therapeutic challenge in a large number of cancer patients. Considering the CDDP side effects in normal tissues, predicting the CDDP response of cancer patients can significantly help to choose the appropriate therapeutic strategy. In this regard, investigating the molecular mechanisms involved in CDDP resistance can lead to the introduction of prognostic markers in cancer patients. Matrix metalloproteinases (MMPs) have critical roles in tissue remodeling and cell migration through extracellular matrix degradation. Therefore, defects in MMPs functions can be associated with tumor metastasis and chemo resistance. In the present review, we discussed the role of MMPs in CDDP response and tumor cell invasion. PubMed, Scopus, Google Scholar, and Web of Science were searched using "MMP", "cisplatin", and "cancer" keywords for data retrieval that was limited to Apr 20, 2024. It has been reported that MMPs can increase CDDP resistance in tumor cells as the effectors of PI3K/AKT, MAPK, and NF-κB signaling pathways or independently through the regulation of structural proteins, autophagy, and epithelial-to-mesenchymal transition (EMT) process. This review has an effective role in introducing MMPs as the prognostic markers and therapeutic targets in CDDP-resistant cancer patients.
顺铂（CDDP）作为最常见的一线化疗药物之一，在治疗广泛的恶性肿瘤中发挥着至关重要的作用。然而，大量癌症患者对 CDDP 产生耐药性，这成为了治疗的挑战。鉴于 CDDP 对正常组织的副作用，预测癌症患者对 CDDP 的反应可以显著帮助选择合适的治疗策略。在这方面，研究 CDDP 耐药性相关的分子机制可以导致癌症患者预后标志物的引入。基质金属蛋白酶（MMPs）通过细胞外基质的降解在组织重塑和细胞迁移中起着关键作用。因此，MMPs 功能的缺陷可能与肿瘤转移和化疗耐药有关。在本综述中，我们讨论了 MMPs 在 CDDP 反应和肿瘤细胞侵袭中的作用。使用 "MMP"、"顺铂" 和 "癌症" 等关键词，在 PubMed、Scopus、Google Scholar 和 Web of Science 上进行了检索，检索时间限制在 2024 年 4 月 20 日。已有报道称，MMPs 可以通过调节结构蛋白、自噬和上皮间质转化（EMT）过程等途径，作为 PI3K/AKT、MAPK 和 NF-κB 信号通路的效应物，或独立地增加肿瘤细胞对 CDDP 的耐药性。本综述在介绍 MMPs 作为 CDDP 耐药性癌症患者的预后标志物和治疗靶点方面具有重要作用。
