Central Research Laboratory, Meenakshi Ammal Dental College, Meenakshi Academy of Higher Education and Research, Maduravoyal, Chennai, 600095, Tamilnadu, India.
Multidisciplinary Research Unit, Chengalpattu Government Medical College, Chengalpattu, 603001, Tamilnadu, India.
Crit Rev Oncol Hematol. 2021 Jun;162:103327. doi: 10.1016/j.critrevonc.2021.103327. Epub 2021 Apr 20.
Cisplatin is the most commonly used first-line drug for cancer treatment. However, many patients develop resistance to cisplatin therapy which ultimately results in therapy failure and increased mortality. A growing body of evidence shows that the hypoxic microenvironment is the prime factor underlying tumor insensitivity to cisplatin treatment. Since tumors in the majority of cancer patients are under hypoxic stress (low oxygen supply), it becomes necessary to understand the pathobiology behind hypoxia-induced cisplatin resistance in cancer cells. Here, we discuss the molecular events that render hypoxic tumors insensitive to cisplatin therapy. Furthermore, various drugs and tumor oxygenation techniques have been developed to circumvent cisplatin resistance in hypoxic tumors. However, their pharmaceutical applications are limited due to failures in clinical investigations and a lack of preclinical studies in the hypoxic tumor microenvironment. This review addresses these challenges and provides new directions for the strategic deployment of cisplatin sensitizers in the hypoxic tumor microenvironment.
顺铂是癌症治疗中最常用的一线药物。然而，许多患者对顺铂治疗产生耐药性，最终导致治疗失败和死亡率增加。越来越多的证据表明，缺氧微环境是肿瘤对顺铂治疗不敏感的主要因素。由于大多数癌症患者的肿瘤处于缺氧应激状态（低氧供应），因此有必要了解缺氧诱导的癌细胞对顺铂耐药的病理生物学机制。在这里，我们讨论了使缺氧肿瘤对顺铂治疗不敏感的分子事件。此外，已经开发了各种药物和肿瘤氧合技术来规避缺氧肿瘤中的顺铂耐药性。然而，由于临床研究中的失败以及在缺氧肿瘤微环境中缺乏临床前研究，它们的药物应用受到限制。这篇综述探讨了这些挑战，并为在缺氧肿瘤微环境中战略部署顺铂增敏剂提供了新的方向。
