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Table of Contents

Breaking Insights

Review

Cancer Research Highlights

Controversy and Consensus

Priority Report

  • Priority Report
    Colorectal Carcinomas Containing Hypermethylated MLH1 Promoter and Wild-Type BRAF/KRAS Are Enriched for Targetable Kinase Fusions
    Emiliano Cocco, Jamal Benhamida, Sumit Middha, Ahmet Zehir, Kerry Mullaney, Jinru Shia, Rona Yaeger, Liying Zhang, Donna Wong, Liliana Villafania, Khedoudja Nafa, Maurizio Scaltriti, Alexander Drilon, Leonard Saltz, Alison M. Schram, Zsofia K. Stadler, David M. Hyman, Ryma Benayed, Marc Ladanyi and Jaclyn F. Hechtman
    Cancer Res March 15 2019 79 (6) 1047-1053; DOI:10.1158/0008-5472.CAN-18-3126

    A high frequency of targetable kinase fusions in BRAF/RAS wild-type, microsatelltie instability-high colorectal carcinoma offers rationale for screening to identify colorectal cancer patients with kinase fusions that may respond to kinase inhibitors.

Genome and Epigenome

  • Genome and Epigenome
    Activation of Estrogen Receptor Alpha by Decitabine Inhibits Osteosarcoma Growth and Metastasis
    Maria Angeles Lillo Osuna, Jesus Garcia-Lopez, Ikbale El Ayachi, Iram Fatima, Aysha B. Khalid, Jerusha Kumpati, Alexandria V. Slayden, Tiffany N. Seagroves, Gustavo A. Miranda-Carboni and Susan A. Krum
    Cancer Res March 15 2019 79 (6) 1054-1068; DOI:10.1158/0008-5472.CAN-18-1255

    These findings describe the effects of DNA methyltransferase inhibition on ERa and its potential role as a tumor suppressor in osteosarcoma.

Metabolism and Chemical Biology

  • Metabolism and Chemical Biology | AuthorChoice
    Mitochondrial miRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription
    Song Fan, Tian Tian, Weixiong Chen, Xiaobin Lv, Xinyuan Lei, Hanqing Zhang, Sheng Sun, Lei Cai, Guokai Pan, Lile He, Zhanpeng Ou, Xinyu Lin, Xinhui Wang, Matthew Francis Perez, Zhiming Tu, Soldano Ferrone, Bakhos A. Tannous and Jinsong Li
    Cancer Res March 15 2019 79 (6) 1069-1084; DOI:10.1158/0008-5472.CAN-18-2505

    These findings uncover a novel mechanism by which mitomiRNA regulates mitochondrial transcription and provide rationale for use of mitomiRNA and mtDNAencoded genes to predict chemosensitivity and patient clinical prognosis.

Molecular Cell Biology

  • Molecular Cell Biology
    Drak/STK17A Drives Neoplastic Glial Proliferation through Modulation of MRLC Signaling
    Alexander S. Chen, Joanna Wardwell-Ozgo, Nilang N. Shah, Deidre Wright, Christina L. Appin, Krishanthan Vigneswaran, Daniel J. Brat, Harley I. Kornblum and Renee D. Read
    Cancer Res March 15 2019 79 (6) 1085-1097; DOI:10.1158/0008-5472.CAN-18-0482

    These findings reveal new insights into differential regulation of cell proliferation in malignant brain tumors, which will have a broader impact on research regarding mechanisms of oncogene cooperation and dependencies in cancer.

  • Molecular Cell Biology
    IFNγ-Induced IFIT5 Promotes Epithelial-to-Mesenchymal Transition in Prostate Cancer via miRNA Processing
    U-Ging Lo, Rey-Chen Pong, Diane Yang, Leah Gandee, Elizabeth Hernandez, Andrew Dang, Chung-Jung Lin, John Santoyo, Shihong Ma, Rajni Sonavane, Jun Huang, Shu-Fen Tseng, Loredana Moro, Arnaldo A. Arbini, Payal Kapur, Ganesh V. Raj, Dalin He, Chih-Ho Lai, Ho Lin and Jer-Tsong Hsieh
    Cancer Res March 15 2019 79 (6) 1098-1112; DOI:10.1158/0008-5472.CAN-18-2207

    A unique IFIT5-XRN1 complex involved in the turnover of specific tumor suppressive microRNAs is the underlying mechanism of IFNγ-induced epithelial-tomesenchymal transition in prostate cancer.

Tumor Biology and Immunology

Translational Science

  • Translational Science | AuthorChoice
    Early Noninvasive Detection of Response to Targeted Therapy in Non–Small Cell Lung Cancer
    Jillian Phallen, Alessandro Leal, Brian D. Woodward, Patrick M. Forde, Jarushka Naidoo, Kristen A. Marrone, Julie R. Brahmer, Jacob Fiksel, Jamie E. Medina, Stephen Cristiano, Doreen N. Palsgrove, Christopher D. Gocke, Daniel C. Bruhm, Parissa Keshavarzian, Vilmos Adleff, Elizabeth Weihe, Valsamo Anagnostou, Robert B. Scharpf, Victor E. Velculescu and Hatim Husain
    Cancer Res March 15 2019 79 (6) 1204-1213; DOI:10.1158/0008-5472.CAN-18-1082

    Cell-free tumor load provides a novel approach for evaluating longitudinal changes in ctDNA during systemic treatment with tyrosine kinase inhibitors and serves an unmet clinical need for real-time, noninvasive detection of tumor response to targeted therapies before radiographic assessment.

  • Translational Science | AuthorChoice
    Dynamics of Tumor and Immune Responses during Immune Checkpoint Blockade in Non–Small Cell Lung Cancer
    Valsamo Anagnostou, Patrick M. Forde, James R. White, Noushin Niknafs, Carolyn Hruban, Jarushka Naidoo, Kristen Marrone, I.K. Ashok Sivakumar, Daniel C. Bruhm, Samuel Rosner, Jillian Phallen, Alessandro Leal, Vilmos Adleff, Kellie N. Smith, Tricia R. Cottrell, Lamia Rhymee, Doreen N. Palsgrove, Christine L. Hann, Benjamin Levy, Josephine Feliciano, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V. Brock, James M. Isbell, Jennifer L. Sauter, Janis Taube, Robert B. Scharpf, Rachel Karchin, Drew M. Pardoll, Jamie E. Chaft, Matthew D. Hellmann, Julie R. Brahmer and Victor E. Velculescu
    Cancer Res March 15 2019 79 (6) 1214-1225; DOI:10.1158/0008-5472.CAN-18-1127

    Rapid and sensitive detection of circulating tumor DNA dynamic changes and T-cell expansion can be used to guide immune targeted therapy for patients with lung cancer.

  • Translational Science | AuthorChoice
    A DNA Repair and Cell-Cycle Gene Expression Signature in Primary and Recurrent Glioblastoma: Prognostic Value and Clinical Implications
    Matthieu Gobin, Petr V. Nazarov, Rolf Warta, Marco Timmer, Guido Reifenberger, Joerg Felsberg, Laurent Vallar, Anthony J. Chalmers, Christel C. Herold-Mende, Roland Goldbrunner, Simone P. Niclou and Eric Van Dyck
    Cancer Res March 15 2019 79 (6) 1226-1238; DOI:10.1158/0008-5472.CAN-18-2076

    These findings suggest that classification of GBM tumors based on a DNA repair and cell-cycle gene expression signature exposes vulnerabilities to standard-ofcare therapies and offers the potential for personalized therapeutic strategies.

  • Translational Science | AuthorChoice
    Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk
    Tao Sun, Rameshwar Patil, Anna Galstyan, Dmytro Klymyshyn, Hui Ding, Alexandra Chesnokova, Webster K. Cavenee, Frank B. Furnari, Vladimir A. Ljubimov, Ekaterina S. Shatalova, Shawn Wagner, Debiao Li, Adam N. Mamelak, Serguei I. Bannykh, Chirag G. Patil, Jeremy D. Rudnick, Jethro Hu, Zachary B. Grodzinski, Arthur Rekechenetskiy, Vida Falahatian, Alexander V. Lyubimov, Yongmei L. Chen, Lai S. Leoh, Tracy R. Daniels-Wells, Manuel L. Penichet, Eggehard Holler, Alexander V. Ljubimov, Keith L. Black and Julia Y. Ljubimova
    Cancer Res March 15 2019 79 (6) 1239-1251; DOI:10.1158/0008-5472.CAN-18-2725

    Laminin-411 expression in the glioma microenvironment correlates with Notch and other cancer stem cell markers and can be targeted by a novel, clinically translatable nanobioconjugate to inhibit glioma growth.

Population and Prevention Science

  • Population and Prevention Science | AuthorChoice
    Epidemiologic and Clinical Analysis of Cervical Cancer Using Data from the Population-Based Osaka Cancer Registry
    Asami Yagi, Yutaka Ueda, Mamoru Kakuda, Yusuke Tanaka, Sayaka Ikeda, Shinya Matsuzaki, Eiji Kobayashi, Toshitaka Morishima, Isao Miyashiro, Keisuke Fukui, Yuri Ito, Tomio Nakayama and Tadashi Kimura
    Cancer Res March 15 2019 79 (6) 1252-1259; DOI:10.1158/0008-5472.CAN-18-3109

    A large cohort analysis of cervical cancer cases reveals that age-adjusted incidence in Japan has increased since 2000 and that age may negatively correlate with resistance to radiation therapy.

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