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Cancer Discovery
Cancer Discovery
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Table of Contents

In This Issue

  • In This Issue
    In This Issue
    Cancer Discov December 1 2020 10 (12) 1775-1779; DOI:10.1158/2159-8290.CD-ITI10-12

In the Spotlight

  • In the Spotlight
    A Sweet Approach to Heat Up Cancer Response to Immunotherapy
    Oliver M.T. Pearce and Heinz Läubli
    Cancer Discov December 1 2020 10 (12) 1789-1790; DOI:10.1158/2159-8290.CD-20-1355

  • In the Spotlight
    BETs Need Greens: Folate Deficiency and Resistance to MYC-Targeted Therapies
    Ludovica Marando and Brian J.P. Huntly
    Cancer Discov December 1 2020 10 (12) 1791-1793; DOI:10.1158/2159-8290.CD-20-1333

  • In the Spotlight
    Histone H3 G34 Tail Mutations in Cancer: Actions in Cis and Trans to Alter Chromatin and Gene Expression
    Jonathan D. Licht
    Cancer Discov December 1 2020 10 (12) 1794-1796; DOI:10.1158/2159-8290.CD-20-1396

Reviews

  • Reviews
    Targeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy
    Sarah-Maria Fendt, Christian Frezza and Ayelet Erez
    Cancer Discov December 1 2020 10 (12) 1797-1807; DOI:10.1158/2159-8290.CD-20-0844

  • Reviews
    Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors
    Dan Sha, Zhaohui Jin, Jan Budczies, Klaus Kluck, Albrecht Stenzinger and Frank A. Sinicrope
    Cancer Discov December 1 2020 10 (12) 1808-1825; DOI:10.1158/2159-8290.CD-20-0522

Research Brief

  • Research Brief
    KEAP1/NFE2L2 Mutations Predict Lung Cancer Radiation Resistance That Can Be Targeted by Glutaminase Inhibition
    Michael S. Binkley, Young-Jun Jeon, Monica Nesselbush, Everett J. Moding, Barzin Y. Nabet, Diego Almanza, Christian Kunder, Henning Stehr, Christopher H. Yoo, Siyeon Rhee, Michael Xiang, Jacob J. Chabon, Emily Hamilton, David M. Kurtz, Linda Gojenola, Susie Grant Owen, Ryan B. Ko, June Ho Shin, Peter G. Maxim, Natalie S. Lui, Leah M. Backhus, Mark F. Berry, Joseph B. Shrager, Kavitha J. Ramchandran, Sukhmani K. Padda, Millie Das, Joel W. Neal, Heather A. Wakelee, Ash A. Alizadeh, Billy W. Loo Jr and Maximilian Diehn
    Cancer Discov December 1 2020 10 (12) 1826-1841; DOI:10.1158/2159-8290.CD-20-0282

    In patients with non–small cell lung cancer, local recurrence following radiotherapy was predicted by loss-of-function KEAP1 mutations or gain-of-function NFE2L2 mutations, and this resistance could be overcome by glutaminase inhibition.

Research Articles

  • Research Articles | AuthorChoice
    Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade
    Qu Zhang, Jia Luo, Song Wu, Han Si, Chen Gao, Wenjing Xu, Shaad E. Abdullah, Brandon W. Higgs, Phillip A. Dennis, Michiel S. van der Heijden, Neil H. Segal, Jamie E. Chaft, Todd Hembrough, J. Carl Barrett and Matthew D. Hellmann
    Cancer Discov December 1 2020 10 (12) 1842-1853; DOI:10.1158/2159-8290.CD-20-0047

    Patients receiving immune checkpoint blockade therapies who had lower circulating tumor DNA (ctDNA) variant allele frequencies on treatment compared with pretreatment had a higher objective response rate and improved overall survival, suggesting that ctDNA analysis may complement existing prognostic techniques.

  • Research Articles
    Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia
    Melissa M. Berrien-Elliott, Amanda F. Cashen, Celia C. Cubitt, Carly C. Neal, Pamela Wong, Julia A. Wagner, Mark Foster, Timothy Schappe, Sweta Desai, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Matthew L. Cooper, Natalia Jaeger, Sridhar Nonavinkere Srivatsan, Feng Gao, Rizwan Romee, Camille N. Abboud, Geoffrey L. Uy, Peter Westervelt, Meagan A. Jacoby, Iskra Pusic, Keith E. Stockerl-Goldstein, Mark A. Schroeder, John DiPersio and Todd A. Fehniger
    Cancer Discov December 1 2020 10 (12) 1854-1871; DOI:10.1158/2159-8290.CD-20-0312

    In patients with acute myeloid leukemia receiving memory-like natural killer (NK)–cell therapy, expression of the inhibitory immune checkpoint receptor NKG2A by the memory-like NK cells was associated with lack of treatment response.

  • Research Articles
    Pharmacologic Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers
    Xinxin Song, Zhuan Zhou, Hongchun Li, Yifan Xue, Xinghua Lu, Ivet Bahar, Oliver Kepp, Mien-Chie Hung, Guido Kroemer and Yong Wan
    Cancer Discov December 1 2020 10 (12) 1872-1893; DOI:10.1158/2159-8290.CD-20-0402

    Preventing glycosylation of the immuno-suppressive transmembrane protein B7-H4 increased its ubiquitination and subsequent degradation, and inhibition of B7-H4 glycosylation in vivo improved immunogenicity of immune-cold tumors.

  • Research Articles
    The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies
    Angela Su, Frank Ling, Camille Vaganay, Gaetano Sodaro, Chaïma Benaksas, Reinaldo Dal Bello, Antoine Forget, Bryann Pardieu, Kevin H. Lin, Justine C. Rutter, Christopher F. Bassil, Gael Fortin, Justine Pasanisi, Iléana Antony-Debré, Gabriela Alexe, Jean-François Benoist, Alain Pruvost, Yana Pikman, Jun Qi, Marie-Hélène Schlageter, Jean-Baptiste Micol, Giovanni Roti, Thomas Cluzeau, Hervé Dombret, Claude Preudhomme, Nina Fenouille, Lina Benajiba, Hava M. Golan, Kimberly Stegmaier, Camille Lobry, Kris C. Wood, Raphael Itzykson and Alexandre Puissant
    Cancer Discov December 1 2020 10 (12) 1894-1911; DOI:10.1158/2159-8290.CD-19-0970

    In vitro and in vivo experiments using models of acute myeloid leukemia showed that the folate cycle enzyme MTHFR mediated response to BET inhibitors, which target oncogenic MYC expression and are in phase I and II clinical trials.

  • Research Articles
    CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade
    Guangchuan Wang, Ryan D. Chow, Lvyun Zhu, Zhigang Bai, Lupeng Ye, Feifei Zhang, Paul A. Renauer, Matthew B. Dong, Xiaoyun Dai, Xiaoya Zhang, Yaying Du, Yujing Cheng, Leilei Niu, Zhiyuan Chu, Kristin Kim, Cun Liao, Paul Clark, Youssef Errami and Sidi Chen
    Cancer Discov December 1 2020 10 (12) 1912-1933; DOI:10.1158/2159-8290.CD-19-1448

    In genetically engineered mouse models, loss-of-function mutations in Kmt2d, which encodes a histone methyltransferase often mutated in human cancers, led to increased anti–PD-1 efficacy against a variety of cancer types.

  • Research Articles
    Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML
    Sheng Li, Xiaowen Chen, Jiahui Wang, Cem Meydan, Jacob L. Glass, Alan H. Shih, Ruud Delwel, Ross L. Levine, Christopher E. Mason and Ari M. Melnick
    Cancer Discov December 1 2020 10 (12) 1934-1949; DOI:10.1158/2159-8290.CD-19-0897

    Mutations that drive acute myeloid leukemia, especially in combination, induced epigenetic alterations prior to leukemogenesis, resulting in epigenetic diversity that was associated with poor prognosis in patients.

  • Research Articles
    Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities
    Marcus R. Kelly, Kaja Kostyrko, Kyuho Han, Nancie A. Mooney, Edwin E. Jeng, Kaitlyn Spees, Phuong T. Dinh, Keene L. Abbott, Dana M. Gwinn, E. Alejandro Sweet-Cordero, Michael C. Bassik and Peter K. Jackson
    Cancer Discov December 1 2020 10 (12) 1950-1967; DOI:10.1158/2159-8290.CD-19-1274

    A new method coupled identification of protein–protein interactions and synthetic-lethal relationships to reveal previously unknown and functionally relevant RAS pathway interactors in mutant KRAS–driven lung adenocarcinoma models.

  • Research Articles | AuthorChoice
    H3.3 G34W Promotes Growth and Impedes Differentiation of Osteoblast-Like Mesenchymal Progenitors in Giant Cell Tumor of Bone
    Sima Khazaei, Nicolas De Jay, Shriya Deshmukh, Liam D. Hendrikse, Wajih Jawhar, Carol C.L. Chen, Leonie G. Mikael, Damien Faury, Dylan M. Marchione, Joel Lanoix, Éric Bonneil, Takeaki Ishii, Siddhant U. Jain, Kateryna Rossokhata, Tianna S. Sihota, Robert Eveleigh, Véronique Lisi, Ashot S. Harutyunyan, Sungmi Jung, Jason Karamchandani, Brendan C. Dickson, Robert Turcotte, Jay S. Wunder, Pierre Thibault, Peter W. Lewis, Benjamin A. Garcia, Stephen C. Mack, Michael D. Taylor, Livia Garzia, Claudia L. Kleinman and Nada Jabado
    Cancer Discov December 1 2020 10 (12) 1968-1987; DOI:10.1158/2159-8290.CD-20-0461

    G34W mutation in histone 3.3, found in most cases of giant cell tumor of bone, caused large-scale epigenetic remodeling that led to aberrant differentiation and recruitment of the giant osteoclasts that underlie the pathologic features of this tumor type.

News in Brief

  • News in Brief
    People
    Cancer Discov December 1 2020 10 (12) 1780-1780; DOI:10.1158/2159-8290.CD-NB2020-091

  • News in Brief
    CAR T-cell Characteristics Determine Efficacy
    Cancer Discov December 1 2020 10 (12) 1780-1780; DOI:10.1158/2159-8290.CD-NB2020-096

  • News in Brief
    Single Mouse Testing Demonstrates Value
    Cancer Discov December 1 2020 10 (12) 1780-1781; DOI:10.1158/2159-8290.CD-NB2020-097

  • News in Brief
    Brain Mural Cells Express CAR T-cell Target
    Cancer Discov December 1 2020 10 (12) 1781-1782; DOI:10.1158/2159-8290.CD-NB2020-095

  • News in Brief
    Nobel Lauds Discovery of Hepatitis C Virus
    Cancer Discov December 1 2020 10 (12) 1782-1782; DOI:10.1158/2159-8290.CD-NB2020-094

  • News in Brief
    Chemistry Nobel Honors CRISPR, an “Essential” Tool for Cancer
    Cancer Discov December 1 2020 10 (12) 1782-1783; DOI:10.1158/2159-8290.CD-NB2020-090

  • News in Brief
    Noted
    Cancer Discov December 1 2020 10 (12) 1783-1783; DOI:10.1158/2159-8290.CD-NB2020-092

  • News in Brief
    Drug Combo May Obviate Chemotherapy in ALL
    Cancer Discov December 1 2020 10 (12) OF1-OF1; DOI:10.1158/2159-8290.CD-NB2020-99

  • News in Brief
    Another KRAS Inhibitor Holds Its Own
    Cancer Discov December 1 2020 10 (12) OF2-OF2; DOI:10.1158/2159-8290.CD-NB2020-098

  • News in Brief
    Abemaciclib Reigns Over Breast Cancer in MonarchE
    Cancer Discov December 1 2020 10 (12) OF3-OF3; DOI:10.1158/2159-8290.CD-NB2020-093

Research Watch

  • Bladder Cancer

    • Research Watch
      Expansion of Mutant Clones Is Widespread in Nonmalignant Urothelium
      Cancer Discov December 1 2020 10 (12) OF11-OF11; DOI:10.1158/2159-8290.CD-RW2020-148

  • Breast Cancer

    • Research Watch
      Imaging Can Identify PI3Kα-Inhibitor Susceptibility in Breast Cancer
      Cancer Discov December 1 2020 10 (12) 1786-1786; DOI:10.1158/2159-8290.CD-RW2020-142

  • Clinical Trials

    • Research Watch
      A Neoantigen Vaccine plus Anti–PD-1 Elicits Antitumor T-cell Responses
      Cancer Discov December 1 2020 10 (12) 1787-1787; DOI:10.1158/2159-8290.CD-RW2020-156

    • Research Watch
      The LSD1 Inhibitor Iadademstat Is Active in Acute Myeloid Leukemia
      Cancer Discov December 1 2020 10 (12) OF4-OF4; DOI:10.1158/2159-8290.CD-RW2020-155

    • Research Watch
      Anti–PD-1 plus a VEGFR2 Inhibitor Shows Promise in Cervical Cancer
      Cancer Discov December 1 2020 10 (12) 1788-1788; DOI:10.1158/2159-8290.CD-RW2020-153

    • Research Watch
      The EZH2 Inhibitor Tazemetostat Shows Efficacy in Follicular Lymphoma
      Cancer Discov December 1 2020 10 (12) 1787-1787; DOI:10.1158/2159-8290.CD-RW2020-150

    • Research Watch
      Intermittent Inhibition of BRAF plus MEK Is Not Beneficial in Melanoma
      Cancer Discov December 1 2020 10 (12) OF7-OF7; DOI:10.1158/2159-8290.CD-RW2020-152

    • Research Watch
      Epithelioid Sarcoma Responds to the Oral EZH2 Inhibitor Tazemetostat
      Cancer Discov December 1 2020 10 (12) OF12-OF12; DOI:10.1158/2159-8290.CD-RW2020-151

    • Research Watch
      Anti–PD-1 plus Chemotherapy Yields 100% Response in Hodgkin Lymphoma
      Cancer Discov December 1 2020 10 (12) 1786-1786; DOI:10.1158/2159-8290.CD-RW2020-145

  • Immunology

    • Research Watch
      Targetable CD4+ T-cell TGFβ Signaling Suppresses Antitumor Immunity
      Cancer Discov December 1 2020 10 (12) 1785-1785; DOI:10.1158/2159-8290.CD-RW2020-158

  • Liver Cancer

    • Research Watch
      Liver Cancer Endothelial and Myeloid Cells Exhibit Fetal Reprogramming
      Cancer Discov December 1 2020 10 (12) 1788-1788; DOI:10.1158/2159-8290.CD-RW2020-141

  • Melanoma

    • Research Watch
      Midkine Promotes Immunosuppression and Reduces Immunotherapy Efficacy
      Cancer Discov December 1 2020 10 (12) OF5-OF5; DOI:10.1158/2159-8290.CD-RW2020-157

  • Metastasis

    • Research Watch
      Tumor Cells Induce Endothelial Cells to Secrete a Chemoattractant
      Cancer Discov December 1 2020 10 (12) 1784-1784; DOI:10.1158/2159-8290.CD-RW2020-146

    • Research Watch
      Neutrophils Provide Lipids to Metastatic Tumor Cells, Fueling Growth
      Cancer Discov December 1 2020 10 (12) OF9-OF9; DOI:10.1158/2159-8290.CD-RW2020-143

  • Molecular Biology

    • Research Watch
      Microsatellite Instability Causes Repeat Expansion and WRN Dependence
      Cancer Discov December 1 2020 10 (12) 1784-1784; DOI:10.1158/2159-8290.CD-RW2020-149

  • Mutations

    • Research Watch
      Somatic Copy-Number Alterations Occur in the Tumor Microenvironment
      Cancer Discov December 1 2020 10 (12) OF6-OF6; DOI:10.1158/2159-8290.CD-RW2020-159

  • Myeloproliferative Neoplasms

    • Research Watch
      Hematopoietic Stem Cell Renewal Drives Myeloproliferative Neoplasms
      Cancer Discov December 1 2020 10 (12) OF8-OF8; DOI:10.1158/2159-8290.CD-RW2020-154

  • Phase Separation

    • Research Watch
      Disease-Linked SHP2 Mutations Cause Phase Separation to Activate MAPK
      Cancer Discov December 1 2020 10 (12) 1785-1785; DOI:10.1158/2159-8290.CD-RW2020-147

  • Senescence

    • Research Watch
      Aging-Related Defects in Oxidative Phosphorylation May Be Tumorigenic
      Cancer Discov December 1 2020 10 (12) OF10-OF10; DOI:10.1158/2159-8290.CD-RW2020-144

Correction

  • Correction | Free Article
    Correction: The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression
    Cancer Discov December 1 2020 10 (12) 1988-1988; DOI:10.1158/2159-8290.CD-20-1573

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Cancer Discovery: 10 (12)
December 2020
Volume 10, Issue 12
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