都柏林大學(xué)研究人員已鑒定出一種新的生物標(biāo)志物，它能鑒定出對(duì)三苯氧胺弱反應(yīng)的乳腺癌患者，三苯氧胺是用于治療乳腺癌的常規(guī)抗激素藥物之一。這將允許臨床醫(yī)生為早期乳腺癌患者量身訂做合適治療方案。
Conway Fellow,，William Gallagher教授與它的研究團(tuán)隊(duì)，他們組成愛爾蘭自然科學(xué)基金戰(zhàn)略研究組--愛爾蘭癌癥分子治療法,，檢測(cè)了1000多個(gè)乳腺癌患者,。他們發(fā)現(xiàn)，相對(duì)于無CART蛋白或低水平CART蛋白的患者,，具有高水平CART（可卡因-苯丙胺調(diào)節(jié)轉(zhuǎn)錄本）蛋白的患者用三苯氧胺治療獲得明顯弱的效果,。
三苯氧胺通過阻斷乳腺癌細(xì)胞內(nèi)雌二醇的生長(zhǎng)啟動(dòng)作用而發(fā)揮藥效。這項(xiàng)研究的結(jié)果發(fā)表在領(lǐng)先的科學(xué)期刊《Oncogene》上，敘述了CART怎樣干涉和阻斷三苯氧胺殺死癌細(xì)胞,。資深科學(xué)家Darran O'Connor博士,，也是研究的共第一作者，他評(píng)論說："鑒定需要額外化療的乳腺癌早期患者具有強(qiáng)烈的臨床意義,。我們相信,，CART譜將使淋巴結(jié)陰性乳腺癌患者容易分層為高風(fēng)險(xiǎn)和低風(fēng)險(xiǎn)類別，從而允許個(gè)性化治療,。"
都柏林大學(xué)醫(yī)學(xué)院國(guó)家產(chǎn)科醫(yī)院的Donal Brennan博士,，也是研究的共第一作者，他補(bǔ)充道,，"我們清楚地指出,，具有高CART表達(dá)腫瘤的絕經(jīng)前與絕經(jīng)后的乳腺癌早期患者用三苯氧胺治療產(chǎn)生弱的療效和不響應(yīng)。
目前,，早期診斷的激素受體陽性,、淋巴結(jié)陰性的乳腺癌患者進(jìn)行外科加抗激素與化療進(jìn)行治療。但是,，當(dāng)前研究顯示,，只采用外科和抗激素治療而不用破壞性的化療，許多患者也獲得相等的療效,。
都柏林大學(xué)研究組與瑞典隆德大學(xué)同事們的共同研究結(jié)果將有助于臨床醫(yī)生精確鑒定不需要化療只需單獨(dú)手術(shù)和抗激素治療就足夠治療癌癥的患者,。除了改善病人的生活質(zhì)量外，這也能減輕相關(guān)的不必要補(bǔ)充治療的經(jīng)濟(jì)負(fù)擔(dān),。
當(dāng)CART作為體重關(guān)鍵調(diào)節(jié)因子與可卡因藥物機(jī)體反應(yīng)的關(guān)鍵調(diào)節(jié)因子而在其他領(lǐng)域被廣泛地研究時(shí),，研究人員首次指出了其與乳腺癌的聯(lián)系。
展望這項(xiàng)研究的未來,，William Gallagher教授,，也是癌癥生物學(xué)副教授、Oncomark公司創(chuàng)始人與首席科學(xué)家,，Oncomark公司為都柏林大學(xué)分子診斷衍生公司,，他說："作為翻譯的研究工作者，我們的目標(biāo)是把實(shí)驗(yàn)室發(fā)現(xiàn)帶到臨床中去?，F(xiàn)在我們的目的是開發(fā)臨床上認(rèn)可的測(cè)試,，使我們能鑒定出那些最受益于量身訂做治療方案的人，這些治療方案依照患者的癌癥CART狀態(tài)而設(shè)計(jì),。（生物谷bioon.com)
doi:10.1038/onc.2011.519
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The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ERα, and is an independent prognostic factor in node-negative breast cancer.
Brennan DJ, O'Connor DP, Laursen H, McGee SF, McCarthy S, Zagozdzon R, Rexhepaj E, Culhane AC, Martin FM, Duffy MJ, Landberg G, Ryden L, Hewitt SM,Kuhar MJ, Bernards R, Millikan RC, Crown JP, Jirstr?m K, Gallagher WM.
Abstract Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n=690; P=0.002, 0.013). We also show that CART increases the transcriptional activity of ERα in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy.
