当前位置:科学网首页 > 小柯机器人 >详情
研究揭示治疗反应异常型癌症的分子特征
作者:小柯机器人 发布时间:2020/11/22 23:50:34

美国国立癌症研究所Louis M. Staudt小组揭示出治疗反应异常型癌症的分子特征。该研究于2020年11月19日在线发表于国际一流学术期刊《癌细胞》。

研究人员使用多种平台分析了来自111名特殊反应患者的无偏倚活检样本,从而揭示了遗传和表观遗传畸变以及肿瘤微环境。综合分析发现了将近四分之一患者治疗反应的合理机制。该机制被分为四大类:DNA损伤反应、细胞内信号转导、免疫参与和有利于预后的遗传改变。这些分析揭示了可用于治疗的合成致死关系以及有利于成功治疗的罕见遗传病灶,同时还提供了有关可影响癌症治疗反应的潜在致癌机制。
 
据悉,一小部分患有晚期疾病的癌症患者比具有同等肿瘤的患者存活时间长得多。通过对个别患者的肿瘤活检进行基因组分析,对治疗产生异常反应的分子机制已被确定。
 
附:英文原文

Title: Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment

Author: David A. Wheeler, Naoko Takebe, Toshinori Hinoue, Katherine A. Hoadley, Maria F. Cardenas, Alina M. Hamilton, Peter W. Laird, Linghua Wang, Adrienne Johnson, Ninad Dewal, Vincent Miller, David Pieyro, Manuel Castro de Moura, Manel Esteller, Hui Shen, Jean Claude Zenklusen, Roy Tarnuzzer, Lisa M. McShane, James V. Tricoli, Paul M. Williams, Irina Lubensky, Geraldine OSullivan-Coyne, Elise C. Kohn, Richard F. Little, Jeffrey White, Shakun Malik, Lyndsay Harris, Carol Weil, Alice P. Chen, Chris Karlovich, Brian Rodgers, Lalitha Shankar, Paula Jacobs, Tracy Nolan, Jianhong Hu, Donna M. Muzny, Harshavardhan Doddapaneni, Viktoriya Korchina, Julie Gastier-Foster, Jay Bowen, Kristen Leraas, Elijah F. Edmondson, James H. Doroshow, Barbara A. Conley, S. Percy Ivy, Louis M. Staudt

Issue&Volume: 2020-11-19

Abstract: A small fraction of cancer patients with advanced disease survive significantly longerthan patients with clinically comparable tumors. Molecular mechanisms for exceptionalresponses to therapy have been identified by genomic analysis of tumor biopsies fromindividual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111exceptional responder patients using multiple platforms to profile genetic and epigeneticaberrations as well as the tumor microenvironment. Integrative analysis uncoveredplausible mechanisms for the therapeutic response in nearly a quarter of the patients.The mechanisms were assigned to four broad categories—DNA damage response, intracellularsignaling, immune engagement, and genetic alterations characteristic of favorableprognosis—with many tumors falling into multiple categories. These analyses revealedsynthetic lethal relationships that may be exploited therapeutically and rare geneticlesions that favor therapeutic success, while also providing a wealth of testablehypotheses regarding oncogenic mechanisms that may influence the response to cancertherapy.

DOI: 10.1016/j.ccell.2020.10.015

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30546-8

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx