Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment

被引：64

作者：

Wheeler, David A. ^{[1
,2
]}

Takebe, Naoko ^{[3
]}

Hinoue, Toshinori ^{[4
]}

Hoadley, Katherine A. ^{[5
]}

Cardenas, Maria F. ^{[1
,2
]}

Hamilton, Alina M. ^{[5
]}

Laird, Peter W. ^{[4
]}

Wang, Linghua ^{[6
]}

Johnson, Adrienne ^{[7
]}

Dewal, Ninad ^{[7
]}

Miller, Vincent ^{[7
]}

Pineyro, David ^{[8
,10
]}

de Moura, Manuel Castro ^{[8
]}

Esteller, Manel ^{[8
,9
,10
,11
]}

Shen, Hui ^{[4
]}

Zenklusen, Jean Claude ^{[12
]}

Tarnuzzer, Roy ^{[12
]}

McShane, Lisa M. ^{[3
]}

Tricoli, James, V ^{[3
]}

Williams, Paul M. ^{[13
]}

Lubensky, Irina ^{[3
]}

O'Sullivan-Coyne, Geraldine ^{[3
]}

Kohn, Elise C. ^{[3
]}

Little, Richard F. ^{[3
]}

White, Jeffrey ^{[3
]}

Malik, Shakun ^{[3
]}

Harris, Lyndsay ^{[3
]}

Weil, Carol ^{[3
]}

Chen, Alice P. ^{[3
]}

Karlovich, Chris ^{[13
]}

Rodgers, Brian ^{[3
]}

Shankar, Lalitha ^{[3
]}

Jacobs, Paula ^{[3
]}

Nolan, Tracy ^{[14
]}

Hu, Jianhong ^{[1
]}

Muzny, Donna M. ^{[1
]}

Doddapaneni, Harshavardhan ^{[1
]}

Korchina, Viktoriya ^{[1
]}

Gastier-Foster, Julie ^{[15
]}

Bowen, Jay ^{[15
]}

Leraas, Kristen ^{[15
]}

Edmondson, Elijah F. ^{[16
]}

Doroshow, James H. ^{[3
]}

Conley, Barbara A. ^{[3
]}

Ivy, S. Percy ^{[3
]}

Staudt, Louis M. ^{[12
]}

机构：

[1] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[3] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA

[4] Van Andel Inst, Grand Rapids, MI 49503 USA

[5] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[7] Fdn Med Inc, Cambridge, MA 02141 USA

[8] Josep Carreras Leukaemia Res Inst, Barcelona 08916, Catalonia, Spain

[9] Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain

[10] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08010, Catalonia, Spain

[11] Univ Barcelona UB, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona 08007, Catalonia, Spain

[12] NCI, Ctr Canc Genom, Bethesda, MD 20892 USA

[13] Frederick Natl Lab Canc Res, Frederick, MD 21701 USA

[14] Univ Arkansas Med Sci, Dept Biomed Informat, Little Rock, AR 72205 USA

[15] Nationwide Childrens Hosp, Columbus, OH 43205 USA

[16] NCI, Pathol & Histol Lab, Frederick Natl Lab Canc Res, NIH, Frederick, MD 21701 USA

来源：

CANCER CELL | 2021年 / 39卷 / 01期

关键词：

CHECKPOINT INHIBITORS; GENOMIC ANALYSIS; CLINICAL-TRIAL; BREAST-CANCER; B-CELLS; DISCOVERY; TEMOZOLOMIDE; EXPRESSION; MUTATIONS; IMMUNOTHERAPY;

D O I：

10.1016/j.ccell.2020.10.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：38 / +

页数：23

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