Maharati Amirhosein, Rajabloo Yasamin, Moghbeli Meysam
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Heliyon. 2024 Dec 25;11(1):e41483. doi: 10.1016/j.heliyon.2024.e41483. eCollection 2025 Jan 15.
Cisplatin (CDDP) is one of the main chemotherapeutic drugs that is widely used in many cancers. However, CDDP resistance is a frequent therapeutic challenge that reduces prognosis in cancer patients. Since, CDDP has noticeable side effects in normal tissues and organs, it is necessary to assess the molecular mechanisms associated with CDDP resistance to improve the therapeutic methods in cancer patients. Drug efflux, detoxifying systems, DNA repair mechanisms, and drug-induced apoptosis are involved in multidrug resistance in CDDP-resistant tumor cells. Mammalian target of rapamycin (mTOR), as a serine/threonine kinase has a pivotal role in various cellular mechanisms such as autophagy, metabolism, drug efflux, and cell proliferation. Although, mTOR is mainly activated by PI3K/AKT pathway, it can also be regulated by many other signaling pathways. PI3K/Akt/mTOR axis functions as a key modulator of drug resistance and unfavorable prognosis in different cancers. Regarding, the pivotal role of mTOR in CDDP response, in the present review we discussed the molecular mechanisms that regulate mTOR mediated CDDP response in tumor cells.
顺铂（CDDP）是广泛应用于多种癌症治疗的主要化疗药物之一。然而，顺铂耐药是一个常见的治疗难题，会降低癌症患者的预后。由于顺铂在正常组织和器官中具有明显的副作用，因此有必要评估与顺铂耐药相关的分子机制，以改进癌症患者的治疗方法。药物外排、解毒系统、DNA修复机制和药物诱导的细胞凋亡都与顺铂耐药肿瘤细胞的多药耐药有关。雷帕霉素靶蛋白（mTOR）作为一种丝氨酸/苏氨酸激酶，在自噬、代谢、药物外排和细胞增殖等各种细胞机制中起关键作用。虽然mTOR主要由PI3K/AKT通路激活，但它也可以被许多其他信号通路调节。PI3K/Akt/mTOR轴在不同癌症中作为耐药和不良预后的关键调节因子发挥作用。鉴于mTOR在顺铂反应中的关键作用，在本综述中，我们讨论了调节mTOR介导的肿瘤细胞顺铂反应的分子机制。
