Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment.
Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment.
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DOI：
10.3389/fonc.2020.554570
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发表时间：
2020
影响因子：
4.7
通讯作者：
Kijima T
中科院分区：
文献类型：
--
作者：
Yoshikawa Y;Kuribayashi K;Minami T;Ohmuraya M;Kijima T
恶性胸膜间皮瘤（MPM）与职业或环境石棉暴露密切相关，并源于胸膜腔中的间皮瘤细胞的肿瘤转化。不可切除MPM的唯一标准初始治疗是顺铂（CDDP）和培美曲塞（PEM）联合化疗。此外，CDDP/PEM是唯一获得批准的具有延长总生存期（OS）证据的方案，尽管接受该方案治疗的患者的中位OS仅为诊断后12个月。因此，新的治疗策略的开发已经研究了大约20年。与个性化肺癌治疗的最新进展相反，间皮瘤的诊断和预后生物标志物研究才刚刚开始。表观遗传改变包括DNA甲基化、组蛋白修饰和其他染色质重塑事件。这些过程涉及许多细胞过程，包括分化、发育和肿瘤发生。表观遗传修饰在与恶性MPM表型和组织学亚型相关的基因表达和调控中起重要作用。根据MERIT研究的结果，免疫检查点PD-1抑制剂nivolumab被批准作为初始化疗失败患者的二线治疗。各种临床免疫治疗试验正在进行中的患者与先进的MPM。在这篇综述中，我们描述了最近的知识表观遗传学的改变，这可能会确定候选的治疗靶点和免疫治疗方案正在开发的MPM。
Malignant pleural mesothelioma (MPM) is strongly associated with occupational or environmental asbestos exposure and arises from neoplastic transformation of mesothelial cells in the pleural cavity. The only standard initial treatment for unresectable MPM is combination chemotherapy with cisplatin (CDDP) and pemetrexed (PEM). Further, CDDP/PEM is the only approved regimen with evidence of prolonged overall survival (OS), although the median OS for patients treated with this regimen is only 12 months after diagnosis. Thus, the development of new therapeutic strategies has been investigated for approximately 20 years. In contrast to recent advances in personalized lung cancer therapies, diagnostic and prognostic biomarker research has just started in mesothelioma. Epigenetic alterations include DNA methylation, histone modifications, and other chromatin-remodeling events. These processes are involved in numerous cellular processes including differentiation, development, and tumorigenesis. Epigenetic modifications play an important role in gene expression and regulation related to malignant MPM phenotypes and histological subtypes. An immune checkpoint PD-1 inhibitor, nivolumab, was approved as second-line therapy for patients who had failed initial chemotherapy, based on the results of the MERIT study. Various clinical immunotherapy trials are ongoing in patients with advanced MPM. In this review, we describe recent knowledge on epigenetic alterations, which might identify candidate therapeutic targets and immunotherapeutic regimens under development for MPM.
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影响因子：
11.2
作者：
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通讯作者：
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作者：
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