Sci Transl Med：病毒性皮肤癌的分子治疗

近日，研究人员在发现一种罕见的皮肤癌病毒的根源四年后，匹兹堡大学癌症研究所（UPCI）大学医学院的研究人员现在已经确定了这种病毒，在动物实验中，可以针对有选择性地激活一个分子杀死肿瘤细胞。这一研究成果将很快被测试患者的治疗。

Moore医学博士说细胞癌（MCC），皮肤癌是常见于中老年人和免疫系统虚弱的人，并且不能轻易诊断出来，它仍然有一个非常差的预后，相关研究论文在5月9日的Science Translational Medicine杂志上。

Moore博士指出：目前我们所做的基因组可以识别癌症的分子原因，然后指出针对性的治疗方式。

在2008年，研究团队第一次描述了新的Merkel细胞多瘤病毒（MCV），Merkel细胞癌。在一年之内，他们发现该病毒对大多数情况下肿瘤发展有作用。Chang博士说：病毒仍然主要存在于皮肤细胞中，并在大多数情况下是没有损害的。但是，当这种病毒​​发生突变时，它可以导致癌症。

doi:10.1126/scitranslmed.3003713
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Survivin Is a Therapeutic Target in Merkel Cell Carcinoma

Reety Arora, Masahiro Shuda, Anna Guastafierro, Huichen Feng, Tuna Toptan, Yanis Tolstov, et al.

Merkel cell polyomavirus (MCV) causes ~80% of primary and metastatic Merkel cell carcinomas (MCCs). By comparing digital transcriptome subtraction deep-sequencing profiles, we found that transcripts of the cellular survivin oncoprotein [BIRC5a (baculoviral inhibitor of apoptosis repeat-containing 5)] were up-regulated sevenfold in virus-positive compared to virus-negative MCC tumors. Knockdown of MCV large T antigen in MCV-positive MCC cell lines decreased survivin mRNA and protein expression. Exogenously expressed MCV large T antigen increased survivin protein expression in non-MCC primary cells. This required an intact retinoblastoma protein–targeting domain that activated survivin gene transcription as well as expression of other G1-S–phase proteins including E2F1 and cyclin E. Survivin expression is critical to the survival of MCV-positive MCC cells. A small-molecule survivin inhibitor, YM155, potently and selectively initiates irreversible, nonapoptotic, programmed MCV-positive MCC cell death. Of 1360 other chemotherapeutic and pharmacologically active compounds screened in vitro, only bortezomib (Velcade) was found to be similarly potent, but was not selective in killing MCV-positive MCC cells. YM155 halted the growth of MCV-positive MCC xenograft tumors and was nontoxic in mice, whereas bortezomib was not active in vivo and mice displayed serious morbidity. Xenograft tumors resumed growth once YM155 treatment was stopped, suggesting that YM155 may be cytostatic rather than cytotoxic in vivo. Identifying the cellular pathways, such as those involving survivin, that are targeted by tumor viruses can lead to rapid and rational identification of drug candidates for treating virus-induced cancers.