Mitochondrial integration and ovarian cancer chemotherapy resistance
Mitochondrial integration and ovarian cancer chemotherapy resistance
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线粒体整合与卵巢癌化疗耐药
DOI：
10.1016/j.yexcr.2021.112549
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Sun Liankun
中科院分区：
文献类型：
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作者：
Shen Luyan;Xia Meihui;Zhang Yu;Luo Haoge;Dong Delu;Sun Liankun
卵巢癌被称为“沉默的杀手”。大多数卵巢癌患者在疾病的晚期阶段首次被诊断出来，因为其早期临床症状不明显。除了早期筛查困难、延误诊断外，卵巢癌患者的高复发率和复发难治性状态也是其死亡率高的重要因素。复发性卵巢癌患者常将新辅助化疗后手术作为首选。然而，这往往伴随着化疗耐药性，导致治疗失败，死亡率超过90%。以往认为以顺铂为代表的化疗药物的抗肿瘤作用完全归因于其对DNA的不可逆损伤，但目前研究发现其可通过核质协同整合抑制细胞生长和细胞毒性。线粒体作为细胞内信号沟通的重要枢纽和整合平台，在肿瘤发生发展过程中参与了代谢重编程、转移能力的获得、化疗药物反应等多个关键因素。线粒体在卵巢癌化疗耐药中的作用越来越被认识到。在这篇综述中，我们讨论了线粒体周围的细胞相互作用的调节网络，阐明了化疗下肿瘤细胞存活的机制，并讨论了干扰线粒体功能作为一种新的抗癌疗法的潜在手段。
Ovarian cancer has been nicknamed the “silent killer”. Most patients with ovarian cancer are diagnosed at an advanced stage of the disease for the first time because of its insignificant early clinical symptoms. In addition to the difficulty of early screening and delay in diagnosis, the high recurrence rate and relapsed refractory status of patients with ovarian cancer are also important factors for their high mortality. Patients with recurrent ovarian cancer often use neoadjuvant chemotherapy followed by surgery as the first choice. However, this is often accompanied by chemotherapy resistance, leading to treatment failure and a mortality rate of more than 90%. In the past, it was believed that the anti-tumor effect of chemotherapeutics represented by cisplatin was entirely attributable to its irreversible damage to DNA, but current research has found that it can inhibit cell growth and cytotoxicity via nuclear and cytoplasmic coordinated integration. As an important hub and integration platform for intracellular signal communication, mitochondria are responsible for multiple key factors during tumor occurrence and development, such as metabolic reprogramming, acquisition of metastatic ability, and chemotherapy drug response. The role of mitochondria in ovarian cancer chemotherapy resistance is becoming increasingly recognized. In this review, we discuss the cellular interactive regulatory network surrounding mitochondria, elucidate the mechanisms of tumor cell survival under chemotherapy, and discuss potential means of interfering with mitochondrial function as a novel anti-cancer therapy.