7月10日，Cancer Cell杂志报道了抑制RNA聚合酶可肿瘤特异性激活p53，从而有望治疗肿瘤。
核糖体RNA基因（rDNA）在RNA聚合酶催化下的转录增加是人类癌症的一个共同特点，但人们仍不清楚它是否是引发恶性表型所必须的。
本研究表明，小分子药物CX-5461（CX-5461是一种有效的小分子rRNA的合成抑制剂）可靶向rDNA转录，从而选择性地杀死体内的B淋巴瘤细胞，同时保持野生型B细胞群体的存活。
该治疗效果是p53依赖的凋亡信号激活和核仁破坏的结果。人类白血病和淋巴瘤细胞株也显示出对于这种依赖于p53基因突变状态的rDNA转录抑制的高敏感性。
这些结果说明，选择性抑制rDNA转录可作为癌症特异性激活p53和治疗恶性血液病的一项有效治疗策略。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53
Megan J. Bywater, Gretchen Poortinga, Elaine Sanij, Nadine Hein, Abigail Peck, Carleen Cullinane, Meaghan Wall, Leonie Cluse, Denis Drygin, Kenna Anderes, Nanni Huser, Chris Proffitt, Joshua Bliesath, Mustapha Haddach, Michael K. Schwaebe, David M. Ryckman, William G. Rice, Clemens Schmitt, Scott W. Lowe, Ricky W. Johnstone, Richard B. Pearson, Grant A. McArthur, Ross D. Hannan
Increased transcription of ribosomal RNA genes (rDNA) by RNA Polymerase I is a common feature of human cancer, but whether it is required for the malignant phenotype remains unclear. We show that rDNA transcription can be therapeutically targeted with the small molecule CX-5461 to selectively kill B-lymphoma cells in vivo while maintaining a viable wild-type B cell population. The therapeutic effect is a consequence of nucleolar disruption and activation of p53-dependent apoptotic signaling. Human leukemia and lymphoma cell lines also show high sensitivity to inhibition of rDNA transcription that is dependent on p53 mutational status. These results identify selective inhibition of rDNA transcription as a therapeutic strategy for the cancer specific activation of p53 and treatment of hematologic malignancies.
