美国科学家在近期出版的《自然·医学》杂志上宣称，他们发现在两种基因中出现的变异会让常用的抗乳腺癌药物——蒽环类抗癌药(Anthracycline)失效，这一突破性发现或可每年挽救数百人的生命。
乳腺癌患者通常会在手术后服用化疗药物来阻止肿瘤扩散或反复，但有些患者却对某类药物具有抗药性。而最新研究结果则可帮助医生根据病人的肿瘤情况制定个性化的治疗方案，大幅提高生存几率。
哈佛医学院附属丹那法波肿瘤研究所的安德烈·理查德森领导的研究团队对85名患者的乳腺癌细胞样本进行了分析。他们发现，在被证明具有抗药性的肿瘤样本中，8号染色体上的某个区域出现了许多额外或者多余的DNA复制片段。
理查德森表示，当该区域内名为LAPTM4B和YWHAZ的两个基因被过度表达时，肿瘤对蒽环类抗癌药产生了抗药性。该药物通常作为辅助疗法给患者服用，有助于抑制患者术后病情反复。
蒽环类抗癌药包括阿霉素、道诺霉素、表阿霉素等，在每年确诊患有乳腺癌的4.6万名英国女性当中，大约有一半人服用这种药物。研究人员还将研究结果同比利时科学家的乳腺癌研究进行了比对，研究证实，拥有这两种基因变异的患者与没有该两种变异的患者相比，恢复情况更差。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
