美國(guó)科學(xué)家在近期出版的《自然·醫(yī)學(xué)》雜志上宣稱,，他們發(fā)現(xiàn)在兩種基因中出現(xiàn)的變異會(huì)讓常用的抗乳腺癌藥物——蒽環(huán)類抗癌藥(Anthracycline)失效，這一突破性發(fā)現(xiàn)或可每年挽救數(shù)百人的生命,。
乳腺癌患者通常會(huì)在手術(shù)后服用化療藥物來(lái)阻止腫瘤擴(kuò)散或反復(fù),，但有些患者卻對(duì)某類藥物具有抗藥性,。而最新研究結(jié)果則可幫助醫(yī)生根據(jù)病人的腫瘤情況制定個(gè)性化的治療方案，大幅提高生存幾率,。
哈佛醫(yī)學(xué)院附屬丹那法波腫瘤研究所的安德烈·理查德森領(lǐng)導(dǎo)的研究團(tuán)隊(duì)對(duì)85名患者的乳腺癌細(xì)胞樣本進(jìn)行了分析,。他們發(fā)現(xiàn)，在被證明具有抗藥性的腫瘤樣本中,，8號(hào)染色體上的某個(gè)區(qū)域出現(xiàn)了許多額外或者多余的DNA復(fù)制片段,。
理查德森表示，當(dāng)該區(qū)域內(nèi)名為L(zhǎng)APTM4B和YWHAZ的兩個(gè)基因被過(guò)度表達(dá)時(shí),，腫瘤對(duì)蒽環(huán)類抗癌藥產(chǎn)生了抗藥性,。該藥物通常作為輔助療法給患者服用，有助于抑制患者術(shù)后病情反復(fù),。
蒽環(huán)類抗癌藥包括阿霉素,、道諾霉素、表阿霉素等,，在每年確診患有乳腺癌的4.6萬(wàn)名英國(guó)女性當(dāng)中,，大約有一半人服用這種藥物。研究人員還將研究結(jié)果同比利時(shí)科學(xué)家的乳腺癌研究進(jìn)行了比對(duì),，研究證實(shí),，擁有這兩種基因變異的患者與沒(méi)有該兩種變異的患者相比，恢復(fù)情況更差,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Medicine 24 January 2010 | doi:10.1038/nm.2090
Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer
Yang Li1,2,9, Lihua Zou1,3,9, Qiyuan Li4,9, Benjamin Haibe-Kains5,6, Ruiyang Tian1, Yan Li1, Christine Desmedt5, Christos Sotiriou5, Zoltan Szallasi4,7, J Dirk Iglehart1,2, Andrea L Richardson1,8,9 & Zhigang Charles Wang1,2,9
Adjuvant chemotherapy for breast cancer after surgery has effectively lowered metastatic recurrence rates1. However, a considerable proportion of women suffer recurrent cancer at distant metastatic sites despite adjuvant treatment. Identification of the genes crucial for tumor response to specific chemotherapy drugs is a challenge but is necessary to improve outcomes2. By using integrated genomics, we identified a small number of overexpressed and amplified genes from chromosome 8q22 that were associated with early disease recurrence despite anthracycline-based adjuvant chemotherapy. We confirmed the association in an analysis of multiple independent cohorts. SiRNA-mediated knockdown of either of two of these genes, the antiapoptotic gene YWHAZ and a lysosomal gene LAPTM4B, sensitized tumor cells to anthracyclines, and overexpression of either of the genes induced anthracycline resistance. Overexpression of LAPTM4B resulted in sequestration of the anthracycline doxorubicin, delaying its appearance in the nucleus. Overexpression of these two genes was associated with poor tumor response to anthracycline treatment in a neoadjuvant chemotherapy trial in women with primary breast cancer. Our results suggest that 8q22 amplification and overexpression of LAPTM4B and YWHAZ contribute to de novo chemoresistance to anthracyclines and are permissive for metastatic recurrence. Overexpression of these two genes may predict anthracycline resistance and influence selection of chemotherapy.
1 Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
2 Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
3 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
4 Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark.
5 Medical Oncology Department, Jules Bordet Institute, Brussels, Belgium.
6 Machine Learning Group, Université Libre de Bruxelles, Brussels, Belgium.
7 Children's Hospital Informatics Program at the Harvard–Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
8 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
9 These authors contributed equally to this work.
