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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 2018 8 (12) 1494-1497; DOI:10.1158/2159-8290.CD-ITI8-12

In the Spotlight

  • In the Spotlight
    Molecular Characterization of Malignant Mesothelioma: Time for New Targets?
    Charu Aggarwal and Steven M. Albelda
    Cancer Discov December 1 2018 8 (12) 1508-1510; DOI:10.1158/2159-8290.CD-18-1181

  • In the Spotlight
    Unleashing Blocked Apoptosis in Cancer Cells: New MCL1 Inhibitors Find Their Groove
    Brian Leber, Justin Kale and David W. Andrews
    Cancer Discov December 1 2018 8 (12) 1511-1514; DOI:10.1158/2159-8290.CD-18-1167

  • In the Spotlight
    TET2 Deficiency Sets the Stage for B-cell Lymphoma
    Jennifer R. Shingleton and Sandeep S. Dave
    Cancer Discov December 1 2018 8 (12) 1515-1517; DOI:10.1158/2159-8290.CD-18-1143

Review

  • Review
    The Clinical Impact of the Genomic Landscape of Mismatch Repair–Deficient Cancers
    Giovanni Germano, Nabil Amirouchene-Angelozzi, Giuseppe Rospo and Alberto Bardelli
    Cancer Discov December 1 2018 8 (12) 1518-1528; DOI:10.1158/2159-8290.CD-18-0150

Research Briefs

  • Research Briefs | AuthorChoice
    Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion
    Zofia Piotrowska, Hideko Isozaki, Jochen K. Lennerz, Justin F. Gainor, Inga T. Lennes, Viola W. Zhu, Nicolas Marcoux, Mandeep K. Banwait, Subba R. Digumarthy, Wenjia Su, Satoshi Yoda, Amanda K. Riley, Varuna Nangia, Jessica J. Lin, Rebecca J. Nagy, Richard B. Lanman, Dora Dias-Santagata, Mari Mino-Kenudson, A. John Iafrate, Rebecca S. Heist, Alice T. Shaw, Erica K. Evans, Corinne Clifford, Sai-Hong I. Ou, Beni Wolf, Aaron N. Hata and Lecia V. Sequist
    Cancer Discov December 1 2018 8 (12) 1529-1539; DOI:10.1158/2159-8290.CD-18-1022

    RET fusions were detected in patients with EGFR-mutant NSCLC who developed resistance to EGFR inhibition, and targeting RET in combination with EGFR inhibition produced responses in two patients.

  • Research Briefs | AuthorChoice
    Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition
    James J. Harding, Maeve A. Lowery, Alan H. Shih, Juan M. Schvartzman, Shengqi Hou, Christopher Famulare, Minal Patel, Mikhail Roshal, Richard K. Do, Ahmet Zehir, Daoqi You, S. Duygu Selcuklu, Agnes Viale, Martin S. Tallman, David M. Hyman, Ed Reznik, Lydia W.S. Finley, Elli Papaemmanuil, Alessandra Tosolini, Mark G. Frattini, Kyle J. MacBeth, Guowen Liu, Bin Fan, Sung Choe, Bin Wu, Yelena Y. Janjigian, Ingo K. Mellinghoff, Luis A. Diaz, Ross L. Levine, Ghassan K. Abou-Alfa, Eytan M. Stein and Andrew M. Intlekofer
    Cancer Discov December 1 2018 8 (12) 1540-1547; DOI:10.1158/2159-8290.CD-18-0877

    IDH1- or IDH2-mutant acute myeloid leukemia and solid tumors can develop resistance to isoform-selective IDH inhibition through mutation of the other IDH isoform.

Research Articles

  • Research Articles | AuthorChoice
    Integrative Molecular Characterization of Malignant Pleural Mesothelioma
    Julija Hmeljak, Francisco Sanchez-Vega, Katherine A. Hoadley, Juliann Shih, Chip Stewart, David Heiman, Patrick Tarpey, Ludmila Danilova, Esther Drill, Ewan A. Gibb, Reanne Bowlby, Rupa Kanchi, Hatice U. Osmanbeyoglu, Yoshitaka Sekido, Jumpei Takeshita, Yulia Newton, Kiley Graim, Manaswi Gupta, Carl M. Gay, Lixia Diao, David L. Gibbs, Vesteinn Thorsson, Lisa Iype, Havish Kantheti, David T. Severson, Gloria Ravegnini, Patrice Desmeules, Achim A. Jungbluth, William D. Travis, Sanja Dacic, Lucian R. Chirieac, Françoise Galateau-Sallé, Junya Fujimoto, Aliya N. Husain, Henrique C. Silveira, Valerie W. Rusch, Robert C. Rintoul, Harvey Pass, Hedy Kindler, Marjorie G. Zauderer, David J. Kwiatkowski, Raphael Bueno, Anne S. Tsao, Jenette Creaney, Tara Lichtenberg, Kristen Leraas, Jay Bowen, TCGA Research Network, Ina Felau, Jean Claude Zenklusen, Rehan Akbani, Andrew D. Cherniack, Lauren A. Byers, Michael S. Noble, Jonathan A. Fletcher, A. Gordon Robertson, Ronglai Shen, Hiroyuki Aburatani, Bruce W. Robinson, Peter Campbell and Marc Ladanyi
    Cancer Discov December 1 2018 8 (12) 1548-1565; DOI:10.1158/2159-8290.CD-18-0804

    Comprehensive, multiplatform genomic analyses of malignant pleural mesothelioma characterize a near-haploid molecular subtype, define prognostic molecular subsets, and identify high expression of VISTA in the epithelioid subtype.

  • Research Articles | AuthorChoice
    A Novel MCL1 Inhibitor Combined with Venetoclax Rescues Venetoclax-Resistant Acute Myelogenous Leukemia
    Haley E. Ramsey, Melissa A. Fischer, Taekyu Lee, Agnieszka E. Gorska, Maria Pia Arrate, Londa Fuller, Kelli L. Boyd, Stephen A. Strickland, John Sensintaffar, Leah J. Hogdal, Gregory D. Ayers, Edward T. Olejniczak, Stephen W. Fesik and Michael R. Savona
    Cancer Discov December 1 2018 8 (12) 1566-1581; DOI:10.1158/2159-8290.CD-18-0140

    An identified MCL1 inhibitor induced apoptosis in AML cells and was safely combined with BCL2 inhibition to overcome BCL2 inhibitor resistance and enhance antitumor activity in mouse models of AML.

  • Research Articles | AuthorChoice
    AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies
    Sean Caenepeel, Sean P. Brown, Brian Belmontes, Gordon Moody, Kathleen S. Keegan, Danny Chui, Douglas A. Whittington, Xin Huang, Leszek Poppe, Alan C. Cheng, Mario Cardozo, Jonathan Houze, Yunxiao Li, Brian Lucas, Nick A. Paras, Xianghong Wang, Joshua P. Taygerly, Marc Vimolratana, Manuel Zancanella, Liusheng Zhu, Elaina Cajulis, Tao Osgood, Jan Sun, Leah Damon, Regina K. Egan, Patricia Greninger, Joseph D. McClanaghan, Jianan Gong, Donia Moujalled, Giovanna Pomilio, Pedro Beltran, Cyril H. Benes, Andrew W. Roberts, David C. Huang, Andrew Wei, Jude Canon, Angela Coxon and Paul E. Hughes
    Cancer Discov December 1 2018 8 (12) 1582-1597; DOI:10.1158/2159-8290.CD-18-0387

    Drug discovery and optimization yielded the selective MCL1 inhibitor AMG 176, which induced apoptosis in cells from hematologic malignancies in vitro and in vivo and could be combined with other therapies.

  • Research Articles
    Exploiting MCL1 Dependency with Combination MEK + MCL1 Inhibitors Leads to Induction of Apoptosis and Tumor Regression in KRAS-Mutant Non–Small Cell Lung Cancer
    Varuna Nangia, Faria M. Siddiqui, Sean Caenepeel, Daria Timonina, Samantha J. Bilton, Nicole Phan, Maria Gomez-Caraballo, Hannah L. Archibald, Chendi Li, Cameron Fraser, Diamanda Rigas, Kristof Vajda, Lorin A. Ferris, Michael Lanuti, Cameron D. Wright, Kevin A. Raskin, Daniel P. Cahill, John H. Shin, Colleen Keyes, Lecia V. Sequist, Zofia Piotrowska, Anna F. Farago, Christopher G. Azzoli, Justin F. Gainor, Kristopher A. Sarosiek, Sean P. Brown, Angela Coxon, Cyril H. Benes, Paul E. Hughes and Aaron N. Hata
    Cancer Discov December 1 2018 8 (12) 1598-1613; DOI:10.1158/2159-8290.CD-18-0277

    Dual inhibition of MCL1 and MEK induces apoptosis and tumor regression in KRAS-mutant models of NSCLC, and BCL-xL inhibition may enhance sensitivity to MCL1 inhibition.

  • Research Articles
    Deletion 6q Drives T-cell Leukemia Progression by Ribosome Modulation
    Stéphanie Gachet, Tiama El-Chaar, David Avran, Eulalia Genesca, Frédéric Catez, Samuel Quentin, Marc Delord, Gabriel Thérizols, Delphine Briot, Godelieve Meunier, Lucie Hernandez, Marika Pla, Willem K. Smits, Jessica G. Buijs-Gladdines, Wouter Van Loocke, Gerben Menschaert, Isabelle André-Schmutz, Tom Taghon, Pieter Van Vlierberghe, Jules P. Meijerink, André Baruchel, Hervé Dombret, Emmanuelle Clappier, Jean-Jacques Diaz, Claude Gazin, Hugues de Thé, François Sigaux and Jean Soulier
    Cancer Discov December 1 2018 8 (12) 1614-1631; DOI:10.1158/2159-8290.CD-17-0831

    SYNCRIP and SNHG5 haploinsufficiency increases leukemic-initiating cell activity and drives del(6q) T-ALL progression by reducing the translation efficiency of transcripts involved in mitochondrial respiration.

  • Research Articles
    TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis
    Pilar M. Dominguez, Hussein Ghamlouch, Wojciech Rosikiewicz, Parveen Kumar, Wendy Béguelin, Lorena Fontán, Martín A. Rivas, Patrycja Pawlikowska, Marine Armand, Enguerran Mouly, Miguel Torres-Martin, Ashley S. Doane, María T. Calvo Fernandez, Matt Durant, Veronique Della-Valle, Matt Teater, Luisa Cimmino, Nathalie Droin, Saber Tadros, Samaneh Motanagh, Alan H. Shih, Mark A. Rubin, Wayne Tam, Iannis Aifantis, Ross L. Levine, Olivier Elemento, Giorgio Inghirami, Michael R. Green, Maria E. Figueroa, Olivier A. Bernard, Said Aoufouchi, Sheng Li, Rita Shaknovich and Ari M. Melnick
    Cancer Discov December 1 2018 8 (12) 1632-1653; DOI:10.1158/2159-8290.CD-18-0657

    Somatic loss-of-function mutation of TET2 reduces enhancer hydroxymethylation to suppress genes that promote exit of B-cells from germinal centers and is a driving event in DLBCL.

News in Brief

  • News in Brief
    People
    Cancer Discov December 1 2018 8 (12) 1498-1498; DOI:10.1158/2159-8290.CD-NB2018-129

  • News in Brief
    NK Cells Respond to Checkpoint Blockade
    Cancer Discov December 1 2018 8 (12) 1498-1498; DOI:10.1158/2159-8290.CD-NB2018-131

  • News in Brief
    Data Offer New Insights into AML
    Cancer Discov December 1 2018 8 (12) 1498-1499; DOI:10.1158/2159-8290.CD-NB2018-147

  • News in Brief
    Resisting CAR T-cell Therapy: A Case Study
    Cancer Discov December 1 2018 8 (12) 1499-1500; DOI:10.1158/2159-8290.CD-NB2018-139

  • News in Brief
    Dacomitinib Approved, but Might Not Be Used
    Cancer Discov December 1 2018 8 (12) 1500-1500; DOI:10.1158/2159-8290.CD-NB2018-138

  • News in Brief
    Combining Biomarkers for Immunotherapy
    Cancer Discov December 1 2018 8 (12) 1500-1501; DOI:10.1158/2159-8290.CD-NB2018-143

  • News in Brief
    SABR Combats Metastatic Disease
    Cancer Discov December 1 2018 8 (12) 1501-1502; DOI:10.1158/2159-8290.CD-NB2018-141

  • News in Brief
    FDA Issues Draft Guidance on MRD Testing
    Cancer Discov December 1 2018 8 (12) 1502-1502; DOI:10.1158/2159-8290.CD-NB2018-145

  • News in Brief
    Noted
    Cancer Discov December 1 2018 8 (12) 1502-1502; DOI:10.1158/2159-8290.CD-NB2018-130

  • News in Brief
    New Classification for Myeloproliferative Neoplasms
    Cancer Discov December 1 2018 8 (12) OF1-OF1; DOI:10.1158/2159-8290.CD-NB2018-144

  • News in Brief
    Cemiplimab Approved for Treatment of CSCC
    Cancer Discov December 1 2018 8 (12) OF2-OF2; DOI:10.1158/2159-8290.CD-NB2018-140

  • News in Brief
    Plasma-Based Genotyping Pays Off in NSCLC
    Cancer Discov December 1 2018 8 (12) OF3-OF3; DOI:10.1158/2159-8290.CD-NB2018-142

  • News in Brief
    Duvelisib Approved for Leukemia, Lymphoma
    Cancer Discov December 1 2018 8 (12) OF4-OF4; DOI:10.1158/2159-8290.CD-NB2018-137

  • News in Brief
    Durvalumab Extends OS in NSCLC
    Cancer Discov December 1 2018 8 (12) OF5-OF5; DOI:10.1158/2159-8290.CD-NB2018-135

  • News in Brief
    ClonoSEQ Cleared for Residual Cancer Testing
    Cancer Discov December 1 2018 8 (12) OF6-OF6; DOI:10.1158/2159-8290.CD-NB2018-136

  • News in Brief
    Charities Fund UK–EU Research Partnerships
    Cancer Discov December 1 2018 8 (12) OF7-OF7; DOI:10.1158/2159-8290.CD-NB2018-132

  • News in Brief
    Technique Pinpoints Oncogenic BRCA1 Mutations
    Cancer Discov December 1 2018 8 (12) OF8-OF8; DOI:10.1158/2159-8290.CD-NB2018-128

  • News in Brief
    NIH Budget Makes Up Ground
    Cancer Discov December 1 2018 8 (12) OF9-OF9; DOI:10.1158/2159-8290.CD-NB2018-134

  • News in Brief
    Study: Atezolizumab Improves Survival in SCLC
    Cancer Discov December 1 2018 8 (12) OF10-OF10; DOI:10.1158/2159-8290.CD-NB2018-133

Research Watch

  • Brain Tumors

    • Research Watch
      ALKBH1 Promotes N6-methyladenine DNA Modifications in Glioblastoma
      Cancer Discov December 1 2018 8 (12) OF11-OF11; DOI:10.1158/2159-8290.CD-RW2018-193

  • Clinical Trials

    • Research Watch
      Vemurafenib Has Activity in Patients with BRAFV600-Mutant Glioma
      Cancer Discov December 1 2018 8 (12) 1507-1507; DOI:10.1158/2159-8290.CD-RW2018-189

    • Research Watch
      Telisotuzumab Vedotin Has Activity in Patients with MET-Positive NSCLC
      Cancer Discov December 1 2018 8 (12) OF12-OF12; DOI:10.1158/2159-8290.CD-RW2018-174

  • DNA Repair

    • Research Watch
      Nuclear cGAS Blocks DNA Repair to Drive Tumorigenesis
      Cancer Discov December 1 2018 8 (12) 1506-1506; DOI:10.1158/2159-8290.CD-RW2018-188

  • Drug Design

    • Research Watch
      A Screen of C2H2 Zinc Fingers Reveals Degrons Targeted by Thalidomide
      Cancer Discov December 1 2018 8 (12) OF13-OF13; DOI:10.1158/2159-8290.CD-RW2018-197

  • Epigenetics

    • Research Watch
      A CDK9 Inhibitor May Suppress Tumor Growth and Enhance Immunotherapy
      Cancer Discov December 1 2018 8 (12) OF14-OF14; DOI:10.1158/2159-8290.CD-RW2018-191

    • Research Watch
      The SWI/SNF Complex Binds to and Inhibits YAP/TAZ
      Cancer Discov December 1 2018 8 (12) 1503-1503; DOI:10.1158/2159-8290.CD-RW2018-195

  • Glioblastoma

    • Research Watch
      A Brain-Penetrant MET Inhibitor Achieves Responses in Glioblastoma
      Cancer Discov December 1 2018 8 (12) OF15-OF15; DOI:10.1158/2159-8290.CD-RW2018-186

  • Hepatocellular Carcinoma

    • Research Watch
      Obesity Independently Drives NASH and Hepatocellular Carcinoma
      Cancer Discov December 1 2018 8 (12) 1505-1505; DOI:10.1158/2159-8290.CD-RW2018-190

  • Immunology

    • Research Watch
      Inhibiting C5a Enhances Chemotherapeutic Efficacy
      Cancer Discov December 1 2018 8 (12) OF16-OF16; DOI:10.1158/2159-8290.CD-RW2018-181

  • Immunotherapy

    • Research Watch
      Neoadjuvant Immune Checkpoint Blockade Has Antitumor Activity
      Cancer Discov December 1 2018 8 (12) 1505-1505; DOI:10.1158/2159-8290.CD-RW2018-178

    • Research Watch
      Mevalonate Pathway Inhibitors May Be Effective Cancer Vaccine Adjuvants
      Cancer Discov December 1 2018 8 (12) OF17-OF17; DOI:10.1158/2159-8290.CD-RW2018-175

    • Research Watch
      Antibody-Dependent Cellular Cytotoxicity Renders Macrophages Immunosuppressive
      Cancer Discov December 1 2018 8 (12) OF18-OF18; DOI:10.1158/2159-8290.CD-RW2018-176

  • Leukemia

    • Research Watch
      LILRB4-Signaling Mediates T-cell Suppression and Leukemia Infiltration
      Cancer Discov December 1 2018 8 (12) OF19-OF19; DOI:10.1158/2159-8290.CD-RW2018-183

    • Research Watch
      RUNX1–ETO Upregulates CCND2 to Drive Leukemogenesis
      Cancer Discov December 1 2018 8 (12) OF20-OF20; DOI:10.1158/2159-8290.CD-RW2018-180

  • Melanoma

    • Research Watch
      MITF Synchronizes UV-Protection Programs in the Skin
      Cancer Discov December 1 2018 8 (12) 1506-1506; DOI:10.1158/2159-8290.CD-RW2018-194

    • Research Watch
      SPRED1 Is a Tumor Suppressor in Mucosal Melanoma
      Cancer Discov December 1 2018 8 (12) 1507-1507; DOI:10.1158/2159-8290.CD-RW2018-196

  • Microbiome

    • Research Watch
      Dysregulated Fermentation of Soluble Fiber May Induce Liver Cancer
      Cancer Discov December 1 2018 8 (12) 1503-1503; DOI:10.1158/2159-8290.CD-RW2018-184

  • Mutations

    • Research Watch
      Transmembrane and Juxtamembrane Domain Mutations Activate HER2
      Cancer Discov December 1 2018 8 (12) 1504-1504; DOI:10.1158/2159-8290.CD-RW2018-192

  • Oncogenes

    • Research Watch
      MYC Interacts with the G9a Methyltransferase to Repress Target Genes
      Cancer Discov December 1 2018 8 (12) OF21-OF21; DOI:10.1158/2159-8290.CD-RW2018-179

  • Ovarian Cancer

    • Research Watch
      IRE1α–XBP1 Suppresses the Antitumor Activity of T Cells
      Cancer Discov December 1 2018 8 (12) OF22-OF22; DOI:10.1158/2159-8290.CD-RW2018-182

  • Prostate Cancer

    • Research Watch
      Oncogenic Epithelial Reprogramming Drives Neuroendocrine Cancers
      Cancer Discov December 1 2018 8 (12) OF23-OF23; DOI:10.1158/2159-8290.CD-RW2018-173

  • Sequencing

    • Research Watch
      Cancer Mutations Occur Frequently in Normal Esophageal Epithelium
      Cancer Discov December 1 2018 8 (12) 1504-1504; DOI:10.1158/2159-8290.CD-RW2018-187

  • Signaling

    • Research Watch
      c-KIT Has a Tumor-Suppressive Role via Induction of Apoptosis
      Cancer Discov December 1 2018 8 (12) OF24-OF24; DOI:10.1158/2159-8290.CD-RW2018-177

  • Transcription

    • Research Watch
      The Super Elongation Complex May Be Targetable in MYC-Driven Tumors
      Cancer Discov December 1 2018 8 (12) OF25-OF25; DOI:10.1158/2159-8290.CD-RW2018-185

Correction

  • Correction | Free Article
    Correction: In Vivo E2F Reporting Reveals Efficacious Schedules of MEK1/2–CDK4/6 Targeting and mTOR–S6 Resistance Mechanisms
    Jessica L.F. Teh, Phil F. Cheng, Timothy J. Purwin, Neda Nikbakht, Prem Patel, Inna Chervoneva, Adam Ertel, Paolo M. Fortina, Ines Kleiber, Kim HooKim, Michael A. Davies, Lawrence N. Kwong, Mitch P. Levesque, Reinhard Dummer and Andrew E. Aplin
    Cancer Discov December 1 2018 8 (12) 1654-1654; DOI:10.1158/2159-8290.CD-18-1291

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Cancer Discovery: 8 (12)
December 2018
Volume 8, Issue 12
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  • In This Issue
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    • Brain Tumors
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    • Leukemia
    • Melanoma
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    • Oncogenes
    • Ovarian Cancer
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