Metallothioneins (MTs) are small cysteine-rich intracellular proteins with four major isoforms identified in mammals, designated MT-1 through MT-4. The best known biological functions of MTs are their ability to bind and sequester metal ions as well as their active role in redox homeostasis. Despite these protective roles, numerous studies have demonstrated that changes in MT expression could be associated with the process of carcinogenesis and participation in cell differentiation, proliferation, migration, and angiogenesis. Hence, MTs have the role of double agents, i.e., working with and against cancer. In view of their rich biochemical properties, it is not surprising that MTs participate in the emergence of chemoresistance in tumor cells. Many studies have demonstrated that MT overexpression is involved in the acquisition of resistance to anticancer drugs including cisplatin, anthracyclines, tyrosine kinase inhibitors and mitomycin. The evidence is gradually increasing for a cellular switch in MT functions, showing that they indeed have two faces: protector and saboteur. Initially, MTs display anti-oncogenic and protective roles; however, once the oncogenic process was launched, MTs are utilized by cancer cells for progression, survival, and contribution to chemoresistance. The duality of MTs can serve as a potential prognostic/diagnostic biomarker and can therefore pave the way towards the development of new cancer treatment strategies. Herein, we review and discuss MTs as tumor disease markers and describe their role in chemoresistance to distinct anticancer drugs.

金属硫蛋白（MTs）是富含半胱氨酸的细胞内小蛋白，在哺乳动物中鉴定出四种主要的亚型，命名为MT-1至MT-4。MTs最著名的生物学功能是它们结合和螯合金属离子的能力以及它们在氧化还原稳态中的积极作用。尽管有这些保护作用，但大量研究表明，MT表达的变化可能与癌变过程以及参与细胞分化，增殖，迁移和血管生成有关。因此，MT具有双重​​代理的作用，即，与癌症抗争。鉴于其丰富的生化特性，MT参与肿瘤细胞化学抗性的出现并不奇怪。许多研究表明，MT的过表达与对包括顺铂，蒽环类，酪氨酸激酶抑制剂和丝裂霉素在内的抗癌药物的耐药性有关。MT功能的蜂窝式转换的证据正在逐渐增加，表明它们确实有两个面孔：保护者和破坏者。最初，MT具有抗癌和保护作用。但是，一旦启动了致癌过程，癌细胞就会利用MT来促进其进展，存活以及对化学耐药性的贡献。MT的双重性可以作为潜在的预后/诊断生物标志物，因此可以为开发新的癌症治疗策略铺平道路。在本文中，我们回顾并讨论了MTs作为肿瘤疾病的标志物，并描述了它们在对不同抗癌药物的化学耐药性中的作用。