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Cancer-selective therapy of the future: apoptin and its mechanism of action.

机译：未来的癌症选择性治疗：凋亡素及其作用机制。

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Classical chemotherapy, that specifically targets rapidly proliferating cells, has been in existence for over eighty years and has proven to be fully successful in only a limited number of cancers. Thus, this review focuses on a novel, emerging approach for cancer therapy that uses alternative, and more unique features of cancer cells. This new approach facilitates the selective targeting of cancer, while sparing normal, non-transformed cells. Examples of molecules that kill cancer cells selectively are: apoptin, E4orf4, viral protein R (VpR), and Brevinin-2R. Below we focus on apoptin, a product of the third open reading frame (VP3) of the chicken anemia virus. Besides discussing apoptin's mechanism of action, we also provide concise insight into the biology of a chicken anemia virus infection. Since apoptin's cancer-selective toxicity depends on its nuclear localization, we broadly discuss mechanism(s) involved in its nuclear retention (both nuclear import and export). We also discuss recent findingson apoptin's molecular mechanism of action, with a focus on the role of Nur77 in apoptin's nucleo-cytoplasmic signaling. Finally, we compare the current findings on apoptin to the mechanism of cancer selective toxicity of E4orf4. In the 'summary' -section, besides highlighting important issues related to cancer-selective therapy, we also discuss concurrent approaches towards therapy personalization, particularly those related to the in vivo-, and real time cancer-therapy efficacy monitoring, using "lab-on-the-chip" and other emerging technologies.
机译：专门针对快速增殖细胞的经典化学疗法已经存在了八十多年，并且仅在有限的几种癌症中被证明是完全成功的。因此，本综述着重于一种新颖的，新兴的癌症治疗方法，该方法使用了癌细胞的替代特征和更多独特特征。这种新方法有助于选择性靶向癌症，同时保留正常的未转化细胞。选择性杀死癌细胞的分子的例子有：凋亡素，E4orf4，病毒蛋白R（VpR）和Brevinin-2R。下面我们重点关注凋亡蛋白，它是鸡贫血病毒的第三个开放阅读框（VP3）的产物。除了讨论细胞凋亡素的作用机理外，我们还提供了对鸡贫血病毒感染生物学的简明见解。由于Apoptin的癌症选择性毒性取决于其核定位，因此我们广泛讨论了涉及其核保留（核进出口）的机制。我们还讨论了有关凋亡蛋白的分子机制的最新发现，重点是Nur77在凋亡蛋白的核质信号传导中的作用。最后，我们将有关凋亡素的当前发现与E4orf4的癌症选择性毒性机制进行了比较。在“摘要”部分中，除了强调与癌症选择性治疗有关的重要问题外，我们还讨论了针对个性化治疗的并行方法，特别是那些与体内和实时癌症治疗效果监测相关的方法，使用“实验室方法”芯片”等新兴技术。

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