当前位置: X-MOL 学术Cancer Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment
Cancer Cell ( IF 48.8 ) Pub Date : 2020-11-19 , DOI: 10.1016/j.ccell.2020.10.015
David A Wheeler 1 , Naoko Takebe 2 , Toshinori Hinoue 3 , Katherine A Hoadley 4 , Maria F Cardenas 1 , Alina M Hamilton 4 , Peter W Laird 3 , Linghua Wang 5 , Adrienne Johnson 6 , Ninad Dewal 6 , Vincent Miller 6 , David Piñeyro 7 , Manuel Castro de Moura 8 , Manel Esteller 9 , Hui Shen 3 , Jean Claude Zenklusen 10 , Roy Tarnuzzer 10 , Lisa M McShane 2 , James V Tricoli 2 , Paul M Williams 11 , Irina Lubensky 2 , Geraldine O'Sullivan-Coyne 2 , Elise C Kohn 2 , Richard F Little 2 , Jeffrey White 2 , Shakun Malik 2 , Lyndsay Harris 2 , Carol Weil 2 , Alice P Chen 2 , Chris Karlovich 11 , Brian Rodgers 2 , Lalitha Shankar 2 , Paula Jacobs 2 , Tracy Nolan 12 , Jianhong Hu 13 , Donna M Muzny 13 , Harshavardhan Doddapaneni 13 , Viktoriya Korchina 13 , Julie Gastier-Foster 14 , Jay Bowen 14 , Kristen Leraas 14 , Elijah F Edmondson 15 , James H Doroshow 2 , Barbara A Conley 2 , S Percy Ivy 2 , Louis M Staudt 10
Affiliation  

A small fraction of cancer patients with advanced disease survive significantly longer than patients with clinically comparable tumors. Molecular mechanisms for exceptional responses to therapy have been identified by genomic analysis of tumor biopsies from individual patients. Here, we analyzed tumor biopsies from an unbiased cohort of 111 exceptional responder patients using multiple platforms to profile genetic and epigenetic aberrations as well as the tumor microenvironment. Integrative analysis uncovered plausible mechanisms for the therapeutic response in nearly a quarter of the patients. The mechanisms were assigned to four broad categories—DNA damage response, intracellular signaling, immune engagement, and genetic alterations characteristic of favorable prognosis—with many tumors falling into multiple categories. These analyses revealed synthetic lethal relationships that may be exploited therapeutically and rare genetic lesions that favor therapeutic success, while also providing a wealth of testable hypotheses regarding oncogenic mechanisms that may influence the response to cancer therapy.



中文翻译:


对治疗表现出特殊反应的癌症的分子特征



一小部分患有晚期疾病的癌症患者的生存时间明显长于具有临床可比肿瘤的患者。通过对个体患者的肿瘤活检进行基因组分析,已经确定了对治疗产生异常反应的分子机制。在这里,我们使用多个平台分析了 111 名特殊反应患者的公正队列的肿瘤活检,以分析遗传和表观遗传畸变以及肿瘤微环境。综合分析揭示了近四分之一患者治疗反应的合理机制。这些机制被分为四大类——DNA损伤反应、细胞内信号传导、免疫参与和良好预后的遗传改变特征——许多肿瘤分为多个类别。这些分析揭示了可用于治疗的综合致死关系和有利于治疗成功的罕见遗传病变,同时还提供了有关可能影响癌症治疗反应的致癌机制的大量可检验的假设。

更新日期:2021-01-11
down
wechat
bug