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首页> 外文期刊>Journal of experimental & clinical cancer research : >Current approach and novel perspectives in nasopharyngeal carcinoma: the role of targeting proteasome dysregulation as a molecular landmark in nasopharyngeal cancer
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Current approach and novel perspectives in nasopharyngeal carcinoma: the role of targeting proteasome dysregulation as a molecular landmark in nasopharyngeal cancer

机译：鼻咽癌的当前方法和新颖的透视：靶向蛋白酶体诱导术中作为鼻咽癌的分子标志的作用

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Nasopharyngeal carcinoma (NPC) represents a molecularly paradigmatic tumor given the complex diversity of environmental as well as host dependent factors that are closely implicated in tissue transformation and carcinogenesis. Epstein Barr Virus (EBV) plays a key role in tissue invasion, hyperplasia and malignant transformation. Therefore, EBV related oncoviral proteins such as Latent Membrane Protein family (LMP1, LMP2), Epstein Barr Nuclear Antigen 1 (EBNA1) and EBV related glycoprotein B (gB) are responsible for inducing intracellular signalling aberrations leading to sustained proliferation and further acquisition of NPC related invasive nature and metastatic potential. Dysregulation of proteasome signaling seems to be centrally implicated in oncoviral protein stabilization as well as in modulating tumor microenvironment. Different studies in vitro and in vivo suggest a potential role of proteasome inhibitors in the therapeutic setting of NPC. Furthermore, alterations affecting proteasome signalling in NPC have been associated to tumor growth and invasion, distant metastasis, immune exclusion and resistance as well as to clinical poor prognosis. So on, recent studies have shown the efficacy of immunotherapy as a suitable therapeutic approach to NPC. Nevertheless, novel strategies seem to look for combinatorial regimens aiming to potentiate immune recognition as well as to restore both primary and acquired immune resistance. In this work, our goal is to thoroughly review the molecular implications of proteasome dysregulation in the molecular pathogenesis of NPC, together with their direct relationship with EBV related oncoviral proteins and their role in promoting immune evasion and resistance. We also aim to hypothesize about the feasibility of the use of proteasome inhibitors as part of immunotherapy-including combinatorial regimens for their potential role in reversing immune resistance and favouring tumor recognition and eventual tumor death.
机译：鼻咽癌（NPC）代表了鉴于环境的复杂多样性以及与组织转化和致癌有关的宿主依赖性因子的复杂多样性的分子范式肿瘤。 Epstein Barr病毒（EBV）在组织侵袭，增生和恶性转化中起着关键作用。因此，EBV相关的内癌血管蛋白如潜伏膜蛋白（LMP1，LMP2），Epstein Barr核抗原1（EBNA1）和EBV相关的糖蛋白B（GB）是诱导细胞内信号传导像畸变，导致持续增殖和进一步收购NPC相关的侵入性质和转移性潜力。蛋白酶体信号传导的失调似乎是卵巢蛋白稳定化以及调节肿瘤微环境的中央。体外和体内的不同研究表明蛋白酶体抑制剂在NPC治疗凝固中的潜在作用。此外，影响NPC中蛋白酶体信号传导的改变与肿瘤生长和侵袭，远处转移，免疫排除和抗性以及临床差的预后相关。因此，最近的研究表明，免疫疗法的疗效作为适当的NPC治疗方法。尽管如此，新的策略似乎寻找旨在增强免疫识别的组合方案，以及恢复初级和获得的免疫抵抗力。在这项工作中，我们的目标是彻底审查蛋白酶体失调在NPC的分子发病机制中的分子影响，以及它们与EBV相关的细胞癌蛋白的直接关系及其在促进免疫逃逸和抗性方面的作用。我们还旨在假设使用蛋白酶体抑制剂的可行性作为免疫疗法的一部分 - 包括组合方案，用于其逆转免疫抗性和倾向于肿瘤识别和最终肿瘤死亡的潜在作用。

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