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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 September 1 2019 9 (9) 1143-1146; DOI:10.1158/2159-8290.CD-ITI9-9

In the Spotlight

  • In the Spotlight
    An “EZ” Epigenetic Road to Leukemia Stem Cell Metabolic Reprogramming?
    Meng Li and Ari M. Melnick
    Cancer Discov September 1 2019 9 (9) 1158-1160; DOI:10.1158/2159-8290.CD-19-0737

  • In the Spotlight
    Epigenetic Control of Fatty-Acid Metabolism Sustains Glioma Stem Cells
    Hayley C. Affronti and Kathryn E. Wellen
    Cancer Discov September 1 2019 9 (9) 1161-1163; DOI:10.1158/2159-8290.CD-19-0733

  • In the Spotlight
    Unconventional T Cells in the Pancreatic Tumor Microenvironment: Thinking Outside the Box
    Sulagna Banerjee, Vikas Dudeja and Ashok Saluja
    Cancer Discov September 1 2019 9 (9) 1164-1166; DOI:10.1158/2159-8290.CD-19-0722

Review

  • Review
    Targeting Autophagy in Cancer: Recent Advances and Future Directions
    Ravi K. Amaravadi, Alec C. Kimmelman and Jayanta Debnath
    Cancer Discov September 1 2019 9 (9) 1167-1181; DOI:10.1158/2159-8290.CD-19-0292

Research Brief

  • Research Brief
    V211D Mutation in MEK1 Causes Resistance to MEK Inhibitors in Colon Cancer
    Yijun Gao, Ann Maria, Na Na, Arnaud da Cruz Paula, Alexander N. Gorelick, Jaclyn F. Hechtman, Julianne Carson, Robert A. Lefkowitz, Britta Weigelt, Barry S. Taylor, HuiYong Zhao, Jorge S. Reis-Filho, Elisa de Stanchina, Neal Rosen, Zhan Yao and Rona Yaeger
    Cancer Discov September 1 2019 9 (9) 1182-1191; DOI:10.1158/2159-8290.CD-19-0356

    A previously uncharacterized mutation in mitogen-activated protein kinase 1 (MEK1) is activating and resistant to allosteric MEK inhibitors, but sensitive to ATP-competitive inhibitors.

Research Articles

  • Research Articles
    Immune Checkpoint Blockade Enhances Shared Neoantigen-Induced T-cell Immunity Directed against Mutated Calreticulin in Myeloproliferative Neoplasms
    Cansu Cimen Bozkus, Vladimir Roudko, John P. Finnigan, John Mascarenhas, Ronald Hoffman, Camelia Iancu-Rubin and Nina Bhardwaj
    Cancer Discov September 1 2019 9 (9) 1192-1207; DOI:10.1158/2159-8290.CD-18-1356

    Myeloproliferative neoplasm–associated calreticulin mutations elicit T-cell responses that can be promoted by immune checkpoint blockade with pembrolizumab.

  • Research Articles
    Interferon Signaling Is Diminished with Age and Is Associated with Immune Checkpoint Blockade Efficacy in Triple-Negative Breast Cancer
    Jaclyn Sceneay, Gregory J. Goreczny, Kristin Wilson, Sara Morrow, Molly J. DeCristo, Jessalyn M. Ubellacker, Yuanbo Qin, Tyler Laszewski, Daniel G. Stover, Victor Barrera, John N. Hutchinson, Rachel A. Freedman, Elizabeth A. Mittendorf and Sandra S. McAllister
    Cancer Discov September 1 2019 9 (9) 1208-1227; DOI:10.1158/2159-8290.CD-18-1454

    Immune dysfunction associated with age in a mouse model of TNBC leads to lack of response to immune checkpoint blockade treatment that can be rescued by the addition of a STING agonist.

  • Research Articles
    Loss of EZH2 Reprograms BCAA Metabolism to Drive Leukemic Transformation
    Zhimin Gu, Yuxuan Liu, Feng Cai, McKenzie Patrick, Jakub Zmajkovic, Hui Cao, Yuannyu Zhang, Alpaslan Tasdogan, Mingyi Chen, Le Qi, Xin Liu, Kailong Li, Junhua Lyu, Kathryn E. Dickerson, Weina Chen, Min Ni, Matthew E. Merritt, Sean J. Morrison, Radek C. Skoda, Ralph J. DeBerardinis and Jian Xu
    Cancer Discov September 1 2019 9 (9) 1228-1247; DOI:10.1158/2159-8290.CD-19-0152

    Knockout of the PRC2 component EZH2 and activating NRAS mutations cooperate to cause MPN progression to leukemia by upregulating the BCAA-metabolism enzyme BCAT1.

  • Research Articles
    Glioma Stem Cell–Specific Superenhancer Promotes Polyunsaturated Fatty-Acid Synthesis to Support EGFR Signaling
    Ryan C. Gimple, Reilly L. Kidwell, Leo J.Y. Kim, Tengqian Sun, Anthony D. Gromovsky, Qiulian Wu, Megan Wolf, Deguan Lv, Shruti Bhargava, Li Jiang, Briana C. Prager, Xiuxing Wang, Qing Ye, Zhe Zhu, Guoxin Zhang, Zhen Dong, Linjie Zhao, Derrick Lee, Junfeng Bi, Andrew E. Sloan, Paul S. Mischel, J. Mark Brown, Hu Cang, Tao Huan, Stephen C. Mack, Qi Xie and Jeremy N. Rich
    Cancer Discov September 1 2019 9 (9) 1248-1267; DOI:10.1158/2159-8290.CD-19-0061

    Glioma stem cells upregulate the polyunsaturated synthesis enzyme ELOVL2, which alters cell-membrane properties and composition to maintain EGFR signaling.

  • Research Articles | AuthorChoice
    Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer
    Timothy J. Humpton, Brinda Alagesan, Gina M. DeNicola, Dan Lu, Georgi N. Yordanov, Carl S. Leonhardt, Melissa A. Yao, Priya Alagesan, Maya N. Zaatari, Youngkyu Park, Jeremy N. Skepper, Kay F. Macleod, Pedro A. Perez-Mancera, Michael P. Murphy, Gerard I. Evan, Karen H. Vousden and David A. Tuveson
    Cancer Discov September 1 2019 9 (9) 1268-1287; DOI:10.1158/2159-8290.CD-18-1409

    Activating Kras mutations cause upregulation of the mitophagy-promoting protein NIX, which alters mitochondrial function and enhances redox capacity to support progression of pancreatic cancer.

  • Research Articles | AuthorChoice
    Innate αβ T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming
    Mautin Hundeyin, Emma Kurz, Ankita Mishra, Juan Andres Kochen Rossi, Shannon M. Liudahl, Kenna R. Leis, Harshita Mehrotra, Mirhee Kim, Luisana E. Torres, Adesola Ogunsakin, Jason Link, Rosalie C. Sears, Shamilene Sivagnanam, Jeremy Goecks, K.M. Sadeq Islam, Igor Dolgalev, Shivraj Savadkar, Wei Wang, Berk Aykut, Joshua Leinwand, Brian Diskin, Salma Adam, Muhammad Israr, Maeliss Gelas, Justin Lish, Kathryn Chin, Mohammad Saad Farooq, Benjamin Wadowski, Jingjing Wu, Suhagi Shah, Dennis O. Adeegbe, Smruti Pushalkar, Varshini Vasudevaraja, Deepak Saxena, Kwok-Kin Wong, Lisa M. Coussens and George Miller
    Cancer Discov September 1 2019 9 (9) 1288-1305; DOI:10.1158/2159-8290.CD-19-0161

    Innate αβ T cells are a significant component of the tumor microenvironment in pancreatic ductal adenocarcinoma and delay tumor growth in mouse and human models.

  • Research Articles | AuthorChoice
    PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage
    Jinfang Zhang, Yu-Ru Lee, Fabin Dang, Wenjian Gan, Archita Venugopal Menon, Jesse M. Katon, Chih-Hung Hsu, John M. Asara, Priyanka Tibarewal, Nicholas R. Leslie, Yang Shi, Pier Paolo Pandolfi and Wenyi Wei
    Cancer Discov September 1 2019 9 (9) 1306-1323; DOI:10.1158/2159-8290.CD-18-0083

    Efficient repair of DNA double-strand breaks depends on NSD2-mediated dimethylation of PTEN and its interaction with p53-binding protein 1.

News in Brief

  • News in Brief
    People
    Cancer Discov September 1 2019 9 (9) 1148-1148; DOI:10.1158/2159-8290.CD-NB2019-080

  • News in Brief
    Call Made to Speed Cell-Therapy Development
    Cancer Discov September 1 2019 9 (9) 1148-1148; DOI:10.1158/2159-8290.CD-NB2019-081

  • News in Brief
    TCR Gene Therapy Improves AML Prognosis
    Cancer Discov September 1 2019 9 (9) 1148-1149; DOI:10.1158/2159-8290.CD-NB2019-083

  • News in Brief
    New Center Takes Aim at Resistance
    Cancer Discov September 1 2019 9 (9) 1149-1149; DOI:10.1158/2159-8290.CD-NB2019-087

  • News in Brief
    CAR T Cells: Hitting the Pause Button
    Cancer Discov September 1 2019 9 (9) 1149-1150; DOI:10.1158/2159-8290.CD-NB2019-086

  • News in Brief
    XPO1 Inhibitor Approved for Multiple Myeloma
    Cancer Discov September 1 2019 9 (9) 1150-1151; DOI:10.1158/2159-8290.CD-NB2019-085

  • News in Brief
    New ADC Shrinks HER2-Positive Tumors
    Cancer Discov September 1 2019 9 (9) 1151-1152; DOI:10.1158/2159-8290.CD-NB2019-089

  • News in Brief
    Researchers Reveal Another KRAS Inhibitor
    Cancer Discov September 1 2019 9 (9) 1152-1152; DOI:10.1158/2159-8290.CD-NB2019-092

  • News in Brief
    Noted
    Cancer Discov September 1 2019 9 (9) 1152-1152; DOI:10.1158/2159-8290.CD-NB2019-079

  • News in Brief
    Vaccine Increases PFS for Metastatic Tumors
    Cancer Discov September 1 2019 9 (9) OF1-OF1; DOI:10.1158/2159-8290.CD-NB2019-091

  • News in Brief
    Blood Test Detects Early-Stage Cancers
    Cancer Discov September 1 2019 9 (9) OF2-OF2; DOI:10.1158/2159-8290.CD-NB2019-090

  • News in Brief
    Novel Therapy Elicits Responses in Pancreatic Cancer
    Cancer Discov September 1 2019 9 (9) OF3-OF3; DOI:10.1158/2159-8290.CD-NB2019-088

  • News in Brief
    CAR T-cell Therapy Yields Durable Remissions in FL
    Cancer Discov September 1 2019 9 (9) OF4-OF4; DOI:10.1158/2159-8290.CD-NB2019-082

  • News in Brief
    BLU-667 Controls RET-Altered Thyroid Cancers
    Cancer Discov September 1 2019 9 (9) OF5-OF5; DOI:10.1158/2159-8290.CD-NB2019-084

Research Watch

  • Bladder Cancer

    • Research Watch
      G9a Inhibition Has Antitumor Activity in Bladder Cancer
      Cancer Discov September 1 2019 9 (9) OF6-OF6; DOI:10.1158/2159-8290.CD-RW2019-105

  • Brain Cancer

    • Research Watch
      A C19MC–LIN28A–MYCN Oncogenic Circuit Drives a Pediatric Brain Cancer
      Cancer Discov September 1 2019 9 (9) OF7-OF7; DOI:10.1158/2159-8290.CD-RW2019-107

  • Breast Cancer

    • Research Watch
      p53 Loss Can Promote Neutrophilia, Increased WNT Signaling, and Metastasis
      Cancer Discov September 1 2019 9 (9) 1156-1156; DOI:10.1158/2159-8290.CD-RW2019-122

    • Research Watch
      Effects on Estrogen Receptor Mobility Underlie Antagonist Activity
      Cancer Discov September 1 2019 9 (9) 1154-1154; DOI:10.1158/2159-8290.CD-RW2019-118

  • Cell Competition

    • Research Watch
      Oxidative Stress Can Shift the Balance of Esophageal Cells
      Cancer Discov September 1 2019 9 (9) 1153-1153; DOI:10.1158/2159-8290.CD-RW2019-115

  • Cell Cycle

    • Research Watch
      The cGAS–STING Pathway Influences Taxane Response
      Cancer Discov September 1 2019 9 (9) OF8-OF8; DOI:10.1158/2159-8290.CD-RW2019-111

  • Cell Death

    • Research Watch
      Hippo Signaling Mediates Ferroptosis in Malignant Mesothelioma
      Cancer Discov September 1 2019 9 (9) 1155-1155; DOI:10.1158/2159-8290.CD-RW2019-119

  • DNA Replication

    • Research Watch
      BRCA1 Phosphorylation and Isomerization Enhances Replication Fork Protection
      Cancer Discov September 1 2019 9 (9) OF9-OF9; DOI:10.1158/2159-8290.CD-RW2019-108

  • Immunology

    • Research Watch
      Tregs Promote Protumor TAM Activity by Suppressing CD8+ T Cells
      Cancer Discov September 1 2019 9 (9) 1155-1155; DOI:10.1158/2159-8290.CD-RW2019-120

  • Immunotherapy

    • Research Watch
      CD24 Is a “Don't Eat Me” Signal That Promotes Tumor Immune Escape
      Cancer Discov September 1 2019 9 (9) 1156-1156; DOI:10.1158/2159-8290.CD-RW2019-123

    • Research Watch
      Expansion of New T Cells May Underlie Response to Immune Checkpoint Blockade
      Cancer Discov September 1 2019 9 (9) OF10-OF10; DOI:10.1158/2159-8290.CD-RW2019-124

    • Research Watch
      ICB Response Is Associated with Pretreatment STAT1 Activation
      Cancer Discov September 1 2019 9 (9) 1153-1153; DOI:10.1158/2159-8290.CD-RW2019-114

    • Research Watch
      The CAR-T Therapy Tisagenlecleucel Is Safe in Secondary CNS Lymphoma
      Cancer Discov September 1 2019 9 (9) OF11-OF11; DOI:10.1158/2159-8290.CD-RW2019-116

    • Research Watch
      TNF-Pathway Proteins Modulate Tumor Susceptibility to T-cell Attack
      Cancer Discov September 1 2019 9 (9) 1157-1157; DOI:10.1158/2159-8290.CD-RW2019-110

    • Research Watch
      Amph-Ligand Vaccine Enhances CAR-T Cell Activity against Solid Tumors
      Cancer Discov September 1 2019 9 (9) 1154-1154; DOI:10.1158/2159-8290.CD-RW2019-112

  • Innate Immunity

    • Research Watch
      HER2 Blocks the cGAS–STING-Mediated Immune Response to DNA Damage
      Cancer Discov September 1 2019 9 (9) OF12-OF12; DOI:10.1158/2159-8290.CD-RW2019-117

  • Leukemia

    • Research Watch
      AML Differentiation Plasticity May Contribute to Relapse
      Cancer Discov September 1 2019 9 (9) 1157-1157; DOI:10.1158/2159-8290.CD-RW2019-121

    • Research Watch
      PARP1 Inhibition Overcomes Immune Escape of Leukemic Stem Cells from NK cells
      Cancer Discov September 1 2019 9 (9) OF13-OF13; DOI:10.1158/2159-8290.CD-RW2019-113

  • Signaling

    • Research Watch
      Structural Analysis of Smoothened Reveals a Sterol Binding Site
      Cancer Discov September 1 2019 9 (9) OF14-OF14; DOI:10.1158/2159-8290.CD-RW2019-106

  • Small-Cell Neuroendocrine Cancer

    • Research Watch
      Phenotypes of SCNCs Originating from Different Tissue Types Converge
      Cancer Discov September 1 2019 9 (9) OF15-OF15; DOI:10.1158/2159-8290.CD-RW2019-109

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Cancer Discovery: 9 (9)
September 2019
Volume 9, Issue 9
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