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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 2017 7 (9) 920-923; DOI:10.1158/2159-8290.CD-ITI7-9

In the Spotlight

  • In the Spotlight | Free Article
    Fast-TRKing Drug Development for Rare Molecular Targets
    Aparna R. Parikh and Ryan B. Corcoran
    Cancer Discov September 1 2017 7 (9) 934-936; DOI:10.1158/2159-8290.CD-17-0704

  • In the Spotlight
    Reversion Mutations with Clinical Use of PARP Inhibitors: Many Genes, Many Versions
    Susan M. Domchek
    Cancer Discov September 1 2017 7 (9) 937-939; DOI:10.1158/2159-8290.CD-17-0734

  • In the Spotlight
    Spotlight on Ibrutinib in PCNSL: Adding Another Feather to Its Cap
    Aparna Lakshmanan and John C. Byrd
    Cancer Discov September 1 2017 7 (9) 940-942; DOI:10.1158/2159-8290.CD-17-0714

Review

  • Review
    New Horizons for Precision Medicine in Biliary Tract Cancers
    Juan W. Valle, Angela Lamarca, Lipika Goyal, Jorge Barriuso and Andrew X. Zhu
    Cancer Discov September 1 2017 7 (9) 943-962; DOI:10.1158/2159-8290.CD-17-0245

Research Briefs

  • Research Briefs | AuthorChoice
    A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion–Positive Solid Tumors
    Alexander Drilon, Ramamoorthy Nagasubramanian, James F. Blake, Nora Ku, Brian B. Tuch, Kevin Ebata, Steve Smith, Veronique Lauriault, Gabrielle R. Kolakowski, Barbara J. Brandhuber, Paul D. Larsen, Karyn S. Bouhana, Shannon L. Winski, Robyn Hamor, Wen-I Wu, Andrew Parker, Tony H. Morales, Francis X. Sullivan, Walter E. DeWolf, Lance A. Wollenberg, Paul R. Gordon, Dorothea N. Douglas-Lindsay, Maurizio Scaltriti, Ryma Benayed, Sandeep Raj, Bethany Hanusch, Alison M. Schram, Philip Jonsson, Michael F. Berger, Jaclyn F. Hechtman, Barry S. Taylor, Steve Andrews, S. Michael Rothenberg and David M. Hyman
    Cancer Discov September 1 2017 7 (9) 963-972; DOI:10.1158/2159-8290.CD-17-0507

    Parallel development of the first-generation TRK TKI larotrectinib with the next-generation TKI LOXO-195 allowed for rapid use of LOXO-195 to treat patients with acquired larotrectinib resistance.

  • Research Briefs
    Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations
    Franklin W. Huang, Juan Miguel Mosquera, Andrea Garofalo, Coyin Oh, Maria Baco, Ali Amin-Mansour, Bokang Rabasha, Samira Bahl, Stephanie A. Mullane, Brian D. Robinson, Saud Aldubayan, Francesca Khani, Beerinder Karir, Eejung Kim, Jeremy Chimene-Weiss, Matan Hofree, Alessandro Romanel, Joseph R. Osborne, Jong Wook Kim, Gissou Azabdaftari, Anna Woloszynska-Read, Karen Sfanos, Angelo M. De Marzo, Francesca Demichelis, Stacey Gabriel, Eliezer M. Van Allen, Jill Mesirov, Pablo Tamayo, Mark A. Rubin, Isaac J. Powell and Levi A. Garraway
    Cancer Discov September 1 2017 7 (9) 973-983; DOI:10.1158/2159-8290.CD-16-0960

    Sequencing of an African-American prostate cancer cohort identified ERF as a tumor suppressor in prostate cancer and shows that increasing ethnic diversity enhances the discovery of potential cancer drivers.

  • Research Briefs | AuthorChoice
    Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
    Olga Kondrashova, Minh Nguyen, Kristy Shield-Artin, Anna V. Tinker, Nelson N.H. Teng, Maria I. Harrell, Michael J. Kuiper, Gwo-Yaw Ho, Holly Barker, Maria Jasin, Rohit Prakash, Elizabeth M. Kass, Meghan R. Sullivan, Gregory J. Brunette, Kara A. Bernstein, Robert L. Coleman, Anne Floquet, Michael Friedlander, Ganessan Kichenadasse, David M. O'Malley, Amit Oza, James Sun, Liliane Robillard, Lara Maloney, David Bowtell; on behalf of the AOCS Study Group, Heidi Giordano, Matthew J. Wakefield, Scott H. Kaufmann, Andrew D. Simmons, Thomas C. Harding, Mitch Raponi, Iain A. McNeish, Elizabeth M. Swisher, Kevin K. Lin and Clare L. Scott
    Cancer Discov September 1 2017 7 (9) 984-998; DOI:10.1158/2159-8290.CD-17-0419

    In patients with high-grade ovarian carcinoma treated with the PARP inhibitor rucaparib, secondary reversion mutations in HR genes restore the open reading frame and HR activity to confer resistance.

  • Research Briefs | AuthorChoice
    Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors
    David Quigley, Joshi J. Alumkal, Alexander W. Wyatt, Vishal Kothari, Adam Foye, Paul Lloyd, Rahul Aggarwal, Won Kim, Eric Lu, Jacob Schwartzman, Kevin Beja, Matti Annala, Rajdeep Das, Morgan Diolaiti, Colin Pritchard, George Thomas, Scott Tomlins, Karen Knudsen, Christopher J. Lord, Charles Ryan, Jack Youngren, Tomasz M. Beer, Alan Ashworth, Eric J. Small and Felix Y. Feng
    Cancer Discov September 1 2017 7 (9) 999-1005; DOI:10.1158/2159-8290.CD-17-0146

    Multiclonal BRCA2 reversion mutations were detected in circulating cell-free DNA from two patients with metastatic prostate cancer after PARP inhibitor treatment, suggesting a mechanism of resistance.

Research Articles

  • Research Articles | AuthorChoice
    Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition
    Jane Goodall, Joaquin Mateo, Wei Yuan, Helen Mossop, Nuria Porta, Susana Miranda, Raquel Perez-Lopez, David Dolling, Dan R. Robinson, Shahneen Sandhu, Gemma Fowler, Berni Ebbs, Penny Flohr, George Seed, Daniel Nava Rodrigues, Gunther Boysen, Claudia Bertan, Mark Atkin, Matthew Clarke, Mateus Crespo, Ines Figueiredo, Ruth Riisnaes, Semini Sumanasuriya, Pasquale Rescigno, Zafeiris Zafeiriou, Adam Sharp, Nina Tunariu, Diletta Bianchini, Alexa Gillman, Christopher J. Lord, Emma Hall, Arul M. Chinnaiyan, Suzanne Carreira and Johann S. de Bono; for the TOPARP-A investigators
    Cancer Discov September 1 2017 7 (9) 1006-1017; DOI:10.1158/2159-8290.CD-17-0261

    Sequencing cfDNA from patients with olaparib-treated prostate cancer reveals that reduced cfDNA is a biomarker of response and can harbor resistance mutations that may guide treatment.

  • Research Articles | AuthorChoice
    Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
    Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. DeAngelis and Ingo K. Mellinghoff
    Cancer Discov September 1 2017 7 (9) 1018-1029; DOI:10.1158/2159-8290.CD-17-0613

    The BTK inhibitor ibrutinib has activity in patients with relapsed or refractory B-cell lymphomas of the CNS, and dual treatment with PI3K/mTOR inhibitors may enhance ibrutinib efficacy in patients with CD79B-mutant tumors.

  • Research Articles
    Discovery and Optimization of HKT288, a Cadherin-6–Targeting ADC for the Treatment of Ovarian and Renal Cancers
    Carl U. Bialucha, Scott D. Collins, Xiao Li, Parmita Saxena, Xiamei Zhang, Clemens Dürr, Bruno Lafont, Pierric Prieur, Yeonju Shim, Rebecca Mosher, David Lee, Lance Ostrom, Tiancen Hu, Sanela Bilic, Ivana Liric Rajlic, Vladimir Capka, Wei Jiang, Joel P. Wagner, GiNell Elliott, Artur Veloso, Jessica C. Piel, Meghan M. Flaherty, Keith G. Mansfield, Emily K. Meseck, Tina Rubic-Schneider, Anne Serdakowski London, William R. Tschantz, Markus Kurz, Duc Nguyen, Aaron Bourret, Matthew J. Meyer, Jason E. Faris, Mary J. Janatpour, Vivien W. Chan, Nicholas C. Yoder, Kalli C. Catcott, Molly A. McShea, Xiuxia Sun, Hui Gao, Juliet Williams, Francesco Hofmann, Jeffrey A. Engelman, Seth A. Ettenberg, William R. Sellers and Emma Lees
    Cancer Discov September 1 2017 7 (9) 1030-1045; DOI:10.1158/2159-8290.CD-16-1414

    The CDH6-targeting antibody–drug conjugate HKT288 causes regression of patient-derived xenografts of CDH6-overexpressing ovarian and renal cancers.

News in Brief

  • News in Brief
    People
    Cancer Discov September 1 2017 7 (9) 924-924; DOI:10.1158/2159-8290.CD-NB2017-102

  • News in Brief
    Panel OKs CAR T Therapy for Leukemia
    Cancer Discov September 1 2017 7 (9) 924-924; DOI:10.1158/2159-8290.CD-NB2017-108

  • News in Brief
    Spreading Colon Cancer Can Bypass Lymph Nodes
    Cancer Discov September 1 2017 7 (9) 924-925; DOI:10.1158/2159-8290.CD-NB2017-106

  • News in Brief
    Biomarker for Antitumor Immunity Identified
    Cancer Discov September 1 2017 7 (9) 925-926; DOI:10.1158/2159-8290.CD-NB2017-104

  • News in Brief
    CAR T Cells Infiltrate Brain, Target Tumors
    Cancer Discov September 1 2017 7 (9) 926-926; DOI:10.1158/2159-8290.CD-NB2017-109

  • News in Brief
    Noted
    Cancer Discov September 1 2017 7 (9) 926-926; DOI:10.1158/2159-8290.CD-NB2017-101

  • News in Brief
    Neratinib Approved for HER2+ Breast Cancer
    Cancer Discov September 1 2017 7 (9) OF1-OF1; DOI:10.1158/2159-8290.CD-NB2017-110

  • News in Brief
    Epacadostat Shows Value in Two SCCHN Trials
    Cancer Discov September 1 2017 7 (9) OF2-OF2; DOI:10.1158/2159-8290.CD-NB2017-100

  • News in Brief
    New Biomarker Identified for PDAC
    Cancer Discov September 1 2017 7 (9) OF3-OF3; DOI:10.1158/2159-8290.CD-NB2017-107

  • News in Brief
    Savolitinib Heads for Phase III Trial in PRCC
    Cancer Discov September 1 2017 7 (9) OF4-OF4; DOI:10.1158/2159-8290.CD-NB2017-105

  • News in Brief
    New SNPs from Testicular Cancer GWAS
    Cancer Discov September 1 2017 7 (9) OF5-OF5; DOI:10.1158/2159-8290.CD-NB2017-103

News in Depth

  • News in Depth
    Why First-Line Nivolumab Is No Better than Chemo
    Cancer Discov September 1 2017 7 (9) 927-927; DOI:10.1158/2159-8290.CD-ND2017-004

  • News in Depth
    Taking the Guesswork Out of Stopping TKIs
    Cancer Discov September 1 2017 7 (9) 928-928; DOI:10.1158/2159-8290.CD-ND2017-005

Research Watch

  • Apoptosis

    • Research Watch
      BAX Can Be Allosterically Sensitized to Promote Apoptosis
      Cancer Discov September 1 2017 7 (9) 933-933; DOI:10.1158/2159-8290.CD-RW2017-136

  • Breast Cancer

    • Research Watch
      Genomic Analysis Detects Recurrent Promoter Mutations in Breast Cancer
      Cancer Discov September 1 2017 7 (9) OF6-OF6; DOI:10.1158/2159-8290.CD-RW2017-130

  • Clinical Trials

    • Research Watch
      Nivolumab Has Antitumor Activity in dMMR/MSI-H Colorectal Cancer
      Cancer Discov September 1 2017 7 (9) 930-930; DOI:10.1158/2159-8290.CD-RW2017-141

    • Research Watch
      Nivolumab Plus Ipilimumab Has Antitumor Activity in Metastatic RCC
      Cancer Discov September 1 2017 7 (9) OF7-OF7; DOI:10.1158/2159-8290.CD-RW2017-132

  • Drug Design

    • Research Watch
      Disrupting the APC–Asef Interaction Suppresses Cancer Cell Migration
      Cancer Discov September 1 2017 7 (9) OF8-OF8; DOI:10.1158/2159-8290.CD-RW2017-145

  • Drug Resistance

    • Research Watch
      Fusobacterium nucleatum Promotes Autophagy-Mediated Chemoresistance
      Cancer Discov September 1 2017 7 (9) 930-930; DOI:10.1158/2159-8290.CD-RW2017-147

    • Research Watch
      GPX4 Blocks Ferroptosis to Drive the Survival of Chemoresistant Cells
      Cancer Discov September 1 2017 7 (9) OF9-OF9; DOI:10.1158/2159-8290.CD-RW2017-134

  • Fanconi Anemia

    • Research Watch
      Biallelic Germline Mutations in RFWD3 May Induce Fanconi Anemia
      Cancer Discov September 1 2017 7 (9) OF10-OF10; DOI:10.1158/2159-8290.CD-RW2017-138

  • Glioblastoma

    • Research Watch
      ASCL1 Promotes Differentiation of Glioblastoma Stem Cells
      Cancer Discov September 1 2017 7 (9) 931-931; DOI:10.1158/2159-8290.CD-RW2017-143

    • Research Watch
      Transcription Elongation Factors Are Potential Targets in Glioblastoma
      Cancer Discov September 1 2017 7 (9) OF11-OF11; DOI:10.1158/2159-8290.CD-RW2017-133

  • Immunotherapy

    • Research Watch
      PTPN2 Loss Sensitizes Tumor Cells to Immunotherapy
      Cancer Discov September 1 2017 7 (9) 932-932; DOI:10.1158/2159-8290.CD-RW2017-148

  • Kinase Inhibitors

    • Research Watch
      Simultaneous Targeting of RAF, MEK, and ERK Limits Drug Resistance
      Cancer Discov September 1 2017 7 (9) 931-931; DOI:10.1158/2159-8290.CD-RW2017-142

  • Lymphoma

    • Research Watch
      CAMKIIγ Stabilizes MYC to Promote T-cell Lymphomagenesis
      Cancer Discov September 1 2017 7 (9) OF12-OF12; DOI:10.1158/2159-8290.CD-RW2017-137

  • Medulloblastoma

    • Research Watch
      Integrative Genomics Characterize Medulloblastoma Subtypes
      Cancer Discov September 1 2017 7 (9) OF13-OF13; DOI:10.1158/2159-8290.CD-RW2017-139

  • Metastasis

    • Research Watch
      FOXA1-Dependent Enhancer Reprogramming Promotes Metastasis
      Cancer Discov September 1 2017 7 (9) OF14-OF14; DOI:10.1158/2159-8290.CD-RW2017-146

  • Neuroblastoma

    • Research Watch
      Core Regulatory Circuitries Mediate Neuroblastoma Heterogeneity
      Cancer Discov September 1 2017 7 (9) 932-932; DOI:10.1158/2159-8290.CD-RW2017-144

    • Research Watch
      Superenhancers Drive Neuroblastoma Differentiation States
      Cancer Discov September 1 2017 7 (9) OF15-OF15; DOI:10.1158/2159-8290.CD-RW2017-129

  • Telomeres

    • Research Watch
      The Telomeric Noncoding RNA TERRA Regulates Telomere Stability
      Cancer Discov September 1 2017 7 (9) 929-929; DOI:10.1158/2159-8290.CD-RW2017-131

  • Translocations

    • Research Watch
      Chromosome Loop Anchors Are Susceptible to DNA Double-Strand Breaks
      Cancer Discov September 1 2017 7 (9) 929-929; DOI:10.1158/2159-8290.CD-RW2017-140

  • Tumor Antigens

    • Research Watch
      Frameshift Indels Generate Highly Immunogenic Tumor Neoantigens
      Cancer Discov September 1 2017 7 (9) 933-933; DOI:10.1158/2159-8290.CD-RW2017-135

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Cancer Discovery: 7 (9)
September 2017
Volume 7, Issue 9
  • Table of Contents
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