6月20日，Sci Transl Med杂志报道了一种很有潜力的治疗皮肤癌的新手段：DNA酶Dz13。
在世界范围内，三分之一的癌症是皮肤相关的，而且皮肤癌在许多人种中的发病率都在增加。研究者发现在小鼠肿瘤模型中，一种靶向c-Jun mRNA的DNA酶，Dz13，可抑制两种常见的皮肤癌：基底细胞和鳞状细胞癌的增长。
研究发现，在免疫缺陷和同系免疫健全小鼠模型中， dz13可抑制肿瘤的生长，并可减少肿瘤转移小鼠模型中肺转移结节的形成。此外，在荷瘤小鼠和斑马鱼中，Dz13抑制新生血管形成并使肿瘤细胞凋亡增加。 dz13对肿瘤生长的抑制，需要一个完整的催化结构域，部分原因是由于肿瘤免疫诱导。
经一系列符合规范的猕猴，小型猪，啮齿动物毒理学研究，这种核酶被认为是安全和耐受性良好的。经过超过70项生理有关体外生物测定证实，Dz13对这些生理指标无影响，说明它具有很小的脱靶效应的倾向。如果这些研究结果，在临床试验中得以证实，Dz13可能提供一种安全，有效治疗人类皮肤癌的手段。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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DNAzyme Targeting c-jun Suppresses Skin Cancer Growth
Hong Cai1, Fernando S. Santiago1, Leonel Prado-Lourenco1, Bo Wang1,*, Margaret Patrikakis1, Miles P. Davenport1, Ghassan J. Maghzal2, Roland Stocker2, Christopher R. Parish3, Beng H. Chong1, Graham J. Lieschke4,?, Tak-Wah Wong5, Colin N. Chesterman1, Douglas J. Francis6, Fergal J. Moloney7,?, Ross St.C. Barnetson7, Gary M. Halliday7 and Levon M. Khachigian
Worldwide, one in three cancers is skin-related, with increasing incidence in many populations. Here, we demonstrate the capacity of a DNAzyme-targeting c-jun mRNA, Dz13, to inhibit growth of two common skin cancer types—basal cell and squamous cell carcinomas—in a therapeutic setting with established tumors. Dz13 inhibited tumor growth in both immunodeficient and immunocompetent syngeneic mice and reduced lung nodule formation in a model of metastasis. In addition, Dz13 suppressed neovascularization in tumor-bearing mice and zebrafish and increased apoptosis of tumor cells. Dz13 inhibition of tumor growth, which required an intact catalytic domain, was due in part to the induction of tumor immunity. In a series of good laboratory practice–compliant toxicology studies in cynomolgus monkeys, minipigs, and rodents, the DNAzyme was found to be safe and well tolerated. It also did not interfere in more than 70 physiologically relevant in vitro bioassays, suggesting a reduced propensity for off-target effects. If these findings hold true in clinical trials, Dz13 may provide a safe, effective therapy for human skin cancer.
