據(jù)英國《每日電訊報(bào)》9月16日（北京時(shí)間）報(bào)道,，美國研究人員研究出了一種藥物，可以阻斷與惡性黑色素瘤密切相關(guān)的B-RAF突變,?？茖W(xué)家認(rèn)為，未來有望研發(fā)出藥物用以主要攻擊與特定腫瘤相關(guān)的基因變異。研究發(fā)表在9月16日出版的《自然》雜志上,。
研究人員表示,，新藥的問世也預(yù)示著制藥公司能夠根據(jù)單個(gè)癌癥病人的基因情況來提供藥物，這些藥物將阻止癌癥惡化并讓目前存在的腫瘤朝良性方向發(fā)展,。也有科學(xué)家稱,，這種藥物的問世可與青霉素的問世相媲美。青霉素作為第一種抗生素,，其發(fā)現(xiàn)是人類醫(yī)藥史上最重大的發(fā)現(xiàn)之一,。
多年來，科學(xué)家一直試圖利用人類基因組計(jì)劃提供的大量遺傳信息來打敗癌癥,，然而,，他們?cè)诎┌Y治療領(lǐng)域取得的進(jìn)展微乎其微，此項(xiàng)發(fā)現(xiàn)應(yīng)是其中最重要的進(jìn)展之一,。
在最新研究中,，美國加州科學(xué)家研發(fā)出的這種藥物能阻斷B-RAF基因突變的影響。B-RAF突變?cè)谥旅缘膼盒院谏亓霾∪酥凶顬槌Ｒ?，但也可在其他諸如胸腺癌,、結(jié)腸癌、子宮癌,、乳腺癌和肺癌等癌癥患者中發(fā)現(xiàn),。
小規(guī)模臨床試驗(yàn)顯示,，參與實(shí)驗(yàn)的具有B-RAF突變的32名病人中,，有24名病人的腫瘤至少減少了30%；并且,，另外有兩名病人的腫瘤完全消失,。
研究人員表示，現(xiàn)在就認(rèn)為這種藥物完全獲得了成功還為時(shí)過早,。該藥物也會(huì)產(chǎn)生一些副作用,，而且，其僅能治療特定的B-RAF突變,。不過,，研究已經(jīng)表明，研發(fā)出同樣針對(duì)特定基因變異（與不同的腫瘤有關(guān)）的藥物非常有潛力,。
目前,，已有一家公司正對(duì)該藥進(jìn)行測試，以診斷出哪個(gè)罹患惡性黑色素瘤的病人擁有B-RAF突變,，且可從該藥物中受益,。
第一個(gè)發(fā)現(xiàn)B-RAF與惡性黑色素瘤有關(guān)的劍橋桑格研究所所長馬克·斯特拉頓表示，應(yīng)該開始從基因的角度來理解癌癥形成的根源。維康基金會(huì)主席馬克·沃爾波特認(rèn)為,，對(duì)于癌癥研究專家來說,，該藥物的問世可與人類發(fā)現(xiàn)青霉素相媲美。不過,，癌癥非常復(fù)雜,，人們還需要對(duì)其展開更進(jìn)一步的研究。（生物谷Bioon.com）
生物谷推薦原文摘要：
Nature doi:10.1038/nature09454
Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
Gideon Bollag1, Peter Hirth1, James Tsai1, Jiazhong Zhang1, Prabha N. Ibrahim1, Hanna Cho1, Wayne Spevak1, Chao Zhang1, Ying Zhang1, Gaston Habets1, Elizabeth A. Burton1, Bernice Wong1, Garson Tsang1, Brian L. West1, Ben Powell1, Rafe Shellooe1, Adhirai Marimuthu1, Hoa Nguyen1, Kam Y. J. Zhang1, Dean R. Artis1, Joseph Schlessinger2, Fei Su3, Brian Higgins3, Raman Iyer3, Kurt D’Andrea4, Astrid Koehler3, Michael Stumm3, Paul S. Lin1, Richard J. Lee3, Joseph Grippo3, Igor Puzanov5, Kevin B. Kim6, Antoni Ribas7, Grant A. McArthur8, Jeffrey A. Sosman5, Paul B. Chapman9, Keith T. Flaherty4, Xiaowei Xu4, Katherine L. Nathanson4 & Keith Nolop1
B-RAF is the most frequently mutated protein kinase in human cancers1. The finding that oncogenic mutations in BRAF are common in melanoma2, followed by the demonstration that these tumours are dependent on the RAF/MEK/ERK pathway3, offered hope that inhibition of B-RAF kinase activity could benefit melanoma patients. Herein, we describe the structure-guided discovery of PLX4032 (RG7204), a potent inhibitor of oncogenic B-RAF kinase activity. Preclinical experiments demonstrated that PLX4032 selectively blocked the RAF/MEK/ERK pathway in BRAF mutant cells and caused regression of BRAF mutant xenografts4. Toxicology studies confirmed a wide safety margin consistent with the high degree of selectivity, enabling Phase 1 clinical trials using a crystalline formulation of PLX4032 (ref. 5). In a subset of melanoma patients, pathway inhibition was monitored in paired biopsy specimens collected before treatment initiation and following two weeks of treatment. This analysis revealed substantial inhibition of ERK phosphorylation, yet clinical evaluation did not show tumour regressions. At higher drug exposures afforded by a new amorphous drug formulation4, 5, greater than 80% inhibition of ERK phosphorylation in the tumours of patients correlated with clinical response. Indeed, the Phase 1 clinical data revealed a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960?mg twice daily5. These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity.
