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Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment

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

  2. Author Address

    Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA., Van Andel Institute, Grand Rapids, MI 49503, USA., Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Foundation Medicine Inc, Cambridge, MA 02141, USA., Josep Carreras Leukaemia Research Institute, Badalona, 08916 Barcelona, Catalonia, Spain; Institucio Catalana de Recerca i Estudis Avan 231;ats (ICREA), 08010 Barcelona, Catalonia, Spain., Josep Carreras Leukaemia Research Institute, Badalona, 08916 Barcelona, Catalonia, Spain., Josep Carreras Leukaemia Research Institute, Badalona, 08916 Barcelona, Catalonia, Spain; Centro de Investigacion Biomedica en Red Cancer (CIBERONC), 28029 Madrid, Spain; Institucio Catalana de Recerca i Estudis Avan 231;ats (ICREA), 08010 Barcelona, Catalonia, Spain; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), 08007 Barcelona, Catalonia, Spain., Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA., Nationwide Children 39;s Hospital, Columbus, OH 43205, USA., Pathology and Histology Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21701, USA., Center for Cancer Genomics, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: lstaudt@mail.nih.gov.,
    1. Year: 2021
    2. Date: Jan 11
    3. Epub Date: 2020 11 16
  2. Journal: Cancer Cell
    1. 39
    2. 1
    3. Pages: 38-53.e7
  4. Type of Article: Article
  5. ISSN: 1535-6108
  1. Abstract:

    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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccell.2020.10.015
  3. PMID: 33217343
  4. View record in Web of Science®
  5. WOS: 000607267600012
  6. PII : S1535-6108(20)30546-8

Library Notes

  1. Fiscal Year: FY2020-2021
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