生物谷报道：美国乔治亚理工学院和卵巢癌研究所的一项新研究显示，一种之前被认为有助于化疗药物杀死癌细胞的基因，事实上可能帮助癌症“茁壮成长”。
研究人员发现，参与研究的70%的卵巢癌患者（其肿瘤中p53基因发生突变）5年后仍然存活。具有正常p53基因的肿瘤患者的5年存活率却只有30％。
这些发现可能为人类抗癌提供一种新的可能策略，即开发一类能够失活接受化疗治疗的患者肿瘤中这种基因功能的药物。这项研究的结果刊登在5月16日的PLoS ONE杂志上。
P53基因长期以来都被认为是指导化疗损伤癌细胞自我毁灭过程中的关键作用因子，但是人们却很少留意到p53在修复受损细胞过程中的作用。
当一个细胞功能受损时，p53基因被活化并试图修复细胞。如果这个细胞不能被修复，那么p53就会启动细胞凋亡程序杀死该细胞。由于p53基因是一个启动细胞凋亡的基因，因此使得癌症研究人员长期以来都认为这种基因对化疗的成功与否至关重要，即p53有助于杀死被化疗治疗所损伤的癌细胞。
但是，在这项最新的试验中，乔治亚理工的研究人员却发现p53可能是一把“双刃剑”。肿瘤中携带突变p53基因的化疗患者，其治疗效果要比具有正常p53基因的患者明显要好。
原始出处:
PLoS ONE
Received: February 20, 2007; Accepted: April 17, 2007; Published: May 16, 2007
Evidence that p53-Mediated Cell-Cycle-Arrest Inhibits Chemotherapeutic Treatment of Ovarian Carcinomas
Carlos S. Moreno1,2, Lilya Matyunina3,4, Erin B. Dickerson3,4, Nina Schubert3,4, Nathan J. Bowen3,4, Sanjay Logani1, Benedict B. Benigno4, John F. McDonald3,4*
1 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America, 2 Winship Cancer Institute, Atlanta, Georgia, United States of America, 3 School of Biology, Georgia Institute of Technology, Atlanta, Georgia, United States of America, 4 Ovarian Cancer Institute, Atlanta, Georgia, United States of America
Abstract
Gene expression profiles of malignant tumors surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L), while the other clusters with non-malignant adenomas (A-L). We show here that although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations, the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships. Our results support a model whereby p53 mediated cell-cycle-arrest/DNA repair serves as a barrier to optimal chemotherapeutic treatment of ovarian and perhaps other carcinomas and suggest that inhibition of p53 during chemotherapy may enhance clinical outcome.
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