生物谷報道：美國喬治亞理工學(xué)院和卵巢癌研究所的一項新研究顯示，一種之前被認(rèn)為有助于化療藥物殺死癌細(xì)胞的基因，事實上可能幫助癌癥“茁壯成長”,。
研究人員發(fā)現(xiàn)，參與研究的70%的卵巢癌患者（其腫瘤中p53基因發(fā)生突變）5年后仍然存活,。具有正常p53基因的腫瘤患者的5年存活率卻只有30％,。
這些發(fā)現(xiàn)可能為人類抗癌提供一種新的可能策略，即開發(fā)一類能夠失活接受化療治療的患者腫瘤中這種基因功能的藥物,。這項研究的結(jié)果刊登在5月16日的PLoS ONE雜志上,。
P53基因長期以來都被認(rèn)為是指導(dǎo)化療損傷癌細(xì)胞自我毀滅過程中的關(guān)鍵作用因子，但是人們卻很少留意到p53在修復(fù)受損細(xì)胞過程中的作用,。
當(dāng)一個細(xì)胞功能受損時,，p53基因被活化并試圖修復(fù)細(xì)胞。如果這個細(xì)胞不能被修復(fù),，那么p53就會啟動細(xì)胞凋亡程序殺死該細(xì)胞,。由于p53基因是一個啟動細(xì)胞凋亡的基因，因此使得癌癥研究人員長期以來都認(rèn)為這種基因?qū)煹某晒εc否至關(guān)重要,，即p53有助于殺死被化療治療所損傷的癌細(xì)胞,。
但是，在這項最新的試驗中,，喬治亞理工的研究人員卻發(fā)現(xiàn)p53可能是一把“雙刃劍”,。腫瘤中攜帶突變p53基因的化療患者，其治療效果要比具有正常p53基因的患者明顯要好,。
原始出處:
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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