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Table of Contents

Breaking Advances

From the Editor's Chair

Reviews

Priority Report

  • Priority Report
    The Cyclic AMP Pathway Is a Sex-Specific Modifier of Glioma Risk in Type I Neurofibromatosis Patients
    Nicole M. Warrington, Tao Sun, Jingqin Luo, Robert C. McKinstry, Patricia C. Parkin, Sara Ganzhorn, Debra Spoljaric, Anne C. Albers, Amanda Merkelson, Douglas R. Stewart, David A. Stevenson, David Viskochil, Todd E. Druley, Jason T. Forys, Karlyne M. Reilly, Michael J. Fisher, Uri Tabori, Jeffrey C. Allen, Joshua D. Schiffman, David H. Gutmann and Joshua B. Rubin
    Cancer Res January 1 2015 75 (1) 16-21; DOI:10.1158/0008-5472.CAN-14-1891

    These results establishing a sex-specific role for cAMP regulation in affecting the risk of gliomas in NF1 patients may offer new rational strategies to reduce risk or treat brain tumors in this population.

Clinical Studies

  • Clinical Studies
    Oncolytic Measles Virus Expressing the Sodium Iodide Symporter to Treat Drug-Resistant Ovarian Cancer
    Evanthia Galanis, Pamela J. Atherton, Matthew J. Maurer, Keith L. Knutson, Sean C. Dowdy, William A. Cliby, Paul Haluska Jr, Harry J. Long, Ann Oberg, Ileana Aderca, Matthew S. Block, Jamie Bakkum-Gamez, Mark J. Federspiel, Stephen J. Russell, Kimberly R. Kalli, Gary Keeney, Kah Whye Peng and Lynn C. Hartmann
    Cancer Res January 1 2015 75 (1) 22-30; DOI:10.1158/0008-5472.CAN-14-2533

    Although clinical application of oncolytic viruses as experimental therapies has frequently been challenged on the grounds of efficacy, more recently engineered vectors based on measles virus may offer effective options to treat certain advanced cancers such as metastatic ovarian cancer.

Integrated Systems and Technologies

Microenvironment and Immunology

  • Microenvironment and Immunology | AuthorChoice
    Akt1 and Akt3 Exert Opposing Roles in the Regulation of Vascular Tumor Growth
    Thuy L. Phung, Wa Du, Qi Xue, Sriram Ayyaswamy, Damien Gerald, Zeus Antonello, Sokha Nhek, Carole A. Perruzzi, Isabel Acevedo, Rajesh Ramanna-Valmiki, Paul Rodriguez-Waitkus, Ladan Enayati, Marcelo L. Hochman, Dina Lev, Sandaruwan Geeganage and Laura E. Benjamin
    Cancer Res January 1 2015 75 (1) 40-50; DOI:10.1158/0008-5472.CAN-13-2961

    These findings offer a preclinical proof of concept for the therapeutic utility of treating poorly understood vascular tumors such as angiosarcoma with S6K inhibitors.

  • Microenvironment and Immunology | AuthorChoice
    Paradoxical Decrease in the Capture and Lymph Node Delivery of Cancer Vaccine Antigen Induced by a TLR4 Agonist as Visualized by Dual-Mode Imaging
    Deepak K. Kadayakkara, Michael J. Korrer, Jeff W.M. Bulte and Hyam I. Levitsky
    Cancer Res January 1 2015 75 (1) 51-61; DOI:10.1158/0008-5472.CAN-14-0820

    An adjuvant molecule that enhances the therapeutic effects of a cancer vaccine was found paradoxically to reduce the efficiency of antigen delivery to lymph nodes, challenging what has been thought to be necessary in an effective adjuvant–at least as formed by expectations from studies of infectious disease vaccines.

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    Tropomodulin 1 Expression Driven by NF-κB Enhances Breast Cancer Growth
    Taku Ito-Kureha, Naohiko Koshikawa, Mizuki Yamamoto, Kentaro Semba, Noritaka Yamaguchi, Tadashi Yamamoto, Motoharu Seiki and Jun-ichiro Inoue
    Cancer Res January 1 2015 75 (1) 62-72; DOI:10.1158/0008-5472.CAN-13-3455

    These findings highlight a novel mechanistic linkage to help explain the NF-κB–dependent malignant phenotype of triple-negative breast cancer, with implications for defining useful theranostic targets in this aggressive disease.

  • Molecular and Cellular Pathobiology
    Twist1 Is a Key Regulator of Cancer-Associated Fibroblasts
    Keun-Woo Lee, So-Young Yeo, Chang Ohk Sung and Seok-Hyung Kim
    Cancer Res January 1 2015 75 (1) 73-85; DOI:10.1158/0008-5472.CAN-14-0350

    Already known as a central contributor to EMT, which drives metastatic progression in cancer cells, the transcription factor Twist1 is also found to function in cancer-associated fibroblasts, where it appears to offer a compelling target to deprogram the tumor-supporting features of the cancer microenvironment.

  • Molecular and Cellular Pathobiology
    Intracellular Osteopontin Inhibits Toll-like Receptor Signaling and Impedes Liver Carcinogenesis
    Xiaoyu Fan, Chunyan He, Wei Jing, Xuyu Zhou, Rui Chen, Lei Cao, Minhui Zhu, Rongjie Jia, Hao Wang, Yajun Guo and Jian Zhao
    Cancer Res January 1 2015 75 (1) 86-97; DOI:10.1158/0008-5472.CAN-14-0615

    Osteopontin is known to act in the tumor microenvironment to promote inflammatory processes that facilitate progression, but this study reveals that it also acts within macrophages that infiltrate budding liver tumors to achieve this end by altering Toll-like receptor signaling.

  • Molecular and Cellular Pathobiology
    PLK1 Phosphorylates PAX3-FOXO1, the Inhibition of Which Triggers Regression of Alveolar Rhabdomyosarcoma
    Verena Thalhammer, Laura A. Lopez-Garcia, David Herrero-Martin, Regina Hecker, Dominik Laubscher, Maria E. Gierisch, Marco Wachtel, Peter Bode, Paolo Nanni, Bernd Blank, Ewa Koscielniak and Beat W. Schäfer
    Cancer Res January 1 2015 75 (1) 98-110; DOI:10.1158/0008-5472.CAN-14-1246

    These findings offer a preclinical proof of concept to target the mitotic kinase PLK1 as a rational strategy to treat an aggressive pediatric tumor.

  • Molecular and Cellular Pathobiology
    LASP1 Is a HIF1α Target Gene Critical for Metastasis of Pancreatic Cancer
    Tiansuo Zhao, He Ren, Jing Li, Jing Chen, Huan Zhang, Wen Xin, Yan Sun, Lei Sun, Yongwei Yang, Junwei Sun, Xiuchao Wang, Song Gao, Chongbiao Huang, Huafeng Zhang, Shengyu Yang and Jihui Hao
    Cancer Res January 1 2015 75 (1) 111-119; DOI:10.1158/0008-5472.CAN-14-2040

    This study identifies a key mediator of metastasis in pancreatic ductal carcinomas that are typically already disseminated at the time of diagnosis, a central challenge in the management of this disease.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology
    VEGF-Targeted Therapy Stably Modulates the Glycolytic Phenotype of Tumor Cells
    Matteo Curtarello, Elisabetta Zulato, Giorgia Nardo, Silvia Valtorta, Giulia Guzzo, Elisabetta Rossi, Giovanni Esposito, Aichi Msaki, Anna Pastò, Andrea Rasola, Luca Persano, Francesco Ciccarese, Roberta Bertorelle, Sergio Todde, Mario Plebani, Henrike Schroer, Stefan Walenta, Wolfgang Mueller-Klieser, Alberto Amadori, Rosa Maria Moresco and Stefano Indraccolo
    Cancer Res January 1 2015 75 (1) 120-133; DOI:10.1158/0008-5472.CAN-13-2037

    These findings suggest that the application of antiangiogenic therapy in cancer selects for metabolic traits of tumors that not only confer treatment resistance but also potentially have a more aggressive character, challenging a central tenet of antiangiogenic therapy as inherently less susceptible to the evolution of resistance.

  • Therapeutics, Targets, and Chemical Biology
    Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma
    Claudia C. Faria, Brian J. Golbourn, Adrian M. Dubuc, Marc Remke, Roberto J. Diaz, Sameer Agnihotri, Amanda Luck, Nesrin Sabha, Samantha Olsen, Xiaochong Wu, Livia Garzia, Vijay Ramaswamy, Stephen C. Mack, Xin Wang, Michael Leadley, Denis Reynaud, Leonardo Ermini, Martin Post, Paul A. Northcott, Stefan M. Pfister, Sidney E. Croul, Marcel Kool, Andrey Korshunov, Christian A. Smith, Michael D. Taylor and James T. Rutka
    Cancer Res January 1 2015 75 (1) 134-146; DOI:10.1158/0008-5472.CAN-13-3629

    These findings provide a strong rationale to clinically evaluate foretinib immediately as a therapy for a defined subset of patients with the most common form of malignant pediatric brain tumor.

  • Therapeutics, Targets, and Chemical Biology
    Cables1 Complex Couples Survival Signaling to the Cell Death Machinery
    Zhi Shi, Hae R. Park, Yuhong Du, Zijian Li, Kejun Cheng, Shi-Yong Sun, Zenggang Li, Haian Fu and Fadlo R. Khuri
    Cancer Res January 1 2015 75 (1) 147-158; DOI:10.1158/0008-5472.CAN-14-0036

    The novel regulatory interface described in this report may offer a new strategy for the development of AKT inhibitors for cancer intervention.

  • Therapeutics, Targets, and Chemical Biology
    Four-in-One Antibodies Have Superior Cancer Inhibitory Activity against EGFR, HER2, HER3, and VEGF through Disruption of HER/MET Crosstalk
    Shi Hu, Wenyan Fu, Weihao Xu, Yang Yang, Melissa Cruz, Sandra D. Berezov, Daniel Jorissen, Hiroaki Takeda and Wangdong Zhu
    Cancer Res January 1 2015 75 (1) 159-170; DOI:10.1158/0008-5472.CAN-14-1670

    These results establish a new principle to achieve combined HER receptor inhibition and limit drug resistance using a single antibody.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Genetic Disruption of Lactate/H+ Symporters (MCTs) and Their Subunit CD147/BASIGIN Sensitizes Glycolytic Tumor Cells to Phenformin
    Ibtissam Marchiq, Renaud Le Floch, Danièle Roux, Marie-Pierre Simon and Jacques Pouyssegur
    Cancer Res January 1 2015 75 (1) 171-180; DOI:10.1158/0008-5472.CAN-14-2260

    This study offers preclinical proof of concept for targeting lactic acid export as a therapeutic approach, the effect of which can be magnified by coupling it with phenformin, an antidiabetic biguanide drug.

  • Therapeutics, Targets, and Chemical Biology
    Mdm2 and Aurora Kinase A Inhibitors Synergize to Block Melanoma Growth by Driving Apoptosis and Immune Clearance of Tumor Cells
    Anna E. Vilgelm, Jeff S. Pawlikowski, Yan Liu, Oriana E. Hawkins, Tyler A. Davis, Jessica Smith, Kevin P. Weller, Linda W. Horton, Colt M. McClain, Gregory D. Ayers, David C. Turner, David C. Essaka, Clinton F. Stewart, Jeffrey A. Sosman, Mark C. Kelley, Jeffrey A. Ecsedy, Jeffrey N. Johnston and Ann Richmond
    Cancer Res January 1 2015 75 (1) 181-193; DOI:10.1158/0008-5472.CAN-14-2405

    These findings offer preclinical proof of concept for a combination drug treatment that leverages both senescence and immune surveillance to improve therapeutic outcomes.

Tumor and Stem Cell Biology

  • Tumor and Stem Cell Biology | AuthorChoice
    Contributions to Drug Resistance in Glioblastoma Derived from Malignant Cells in the Sub-Ependymal Zone
    Sara G.M. Piccirillo, Inmaculada Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J. Price, Richard Heywood, Nicola-Jane Francis, Karen D. Howarth, Vincent P. Collins, Ashok R. Venkitaraman, Christina Curtis, John C. Marioni, Simon Tavaré and Colin Watts
    Cancer Res January 1 2015 75 (1) 194-202; DOI:10.1158/0008-5472.CAN-13-3131

    A particular region of the adult brain analogous to the embryonic forebrain germinal zone, which harbors various neural stem cell populations, is discovered in glioblastoma patients to harbor tumor-initiating cells, identifying this region as a target for immediate therapeutic attention by neuro-oncologists.

  • Tumor and Stem Cell Biology | AuthorChoice
    α-Tubulin Acetylation Elevated in Metastatic and Basal-like Breast Cancer Cells Promotes Microtentacle Formation, Adhesion, and Invasive Migration
    Amanda E. Boggs, Michele I. Vitolo, Rebecca A. Whipple, Monica S. Charpentier, Olga G. Goloubeva, Olga B. Ioffe, Kimberly C. Tuttle, Jana Slovic, Yiling Lu, Gordon B. Mills and Stuart S. Martin
    Cancer Res January 1 2015 75 (1) 203-215; DOI:10.1158/0008-5472.CAN-13-3563

    These results identify a tight correlation between acetylated α-tubulin levels and aggressive metastatic behavior in breast cancer, with potential implications for the definition of a simple prognostic biomarker in patients with basal-like breast cancers.

  • Tumor and Stem Cell Biology
    B-Raf Inhibitors Induce Epithelial Differentiation in BRAF-Mutant Colorectal Cancer Cells
    Ricarda Herr, Martin Köhler, Hana Andrlová, Florian Weinberg, Yvonne Möller, Sebastian Halbach, Lisa Lutz, Justin Mastroianni, Martin Klose, Nicola Bittermann, Silke Kowar, Robert Zeiser, Monilola A. Olayioye, Silke Lassmann, Hauke Busch, Melanie Boerries and Tilman Brummer
    Cancer Res January 1 2015 75 (1) 216-229; DOI:10.1158/0008-5472.CAN-13-3686

    This article reveals a novel facet of BRAF and MEK inhibitors in triggering differentiation of colorectal tumors, providing a mechanistic rationale to immediately evaluate them clinically as antimetastatic agents in this setting.

  • Tumor and Stem Cell Biology
    SYK Is a Candidate Kinase Target for the Treatment of Advanced Prostate Cancer
    Veerander P.S. Ghotra, Shuning He, Geertje van der Horst, Steffen Nijhoff, Hans de Bont, Annemarie Lekkerkerker, Richard Janssen, Guido Jenster, Geert J.L.H. van Leenders, A. Marije M. Hoogland, Esther I. Verhoef, Zuzanna Baranski, Jiangling Xiong, Bob van de Water, Gabri van der Pluijm, B. Ewa Snaar-Jagalska and Erik H.J. Danen
    Cancer Res January 1 2015 75 (1) 230-240; DOI:10.1158/0008-5472.CAN-14-0629

    These striking preclinical findings offer a mechanistic rationale to immediately reposition SYK kinase inhibitors currently in early clinical trials for evaluation in patients with metastatic prostate cancer.

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Cancer Research: 75 (1)
January 2015
Volume 75, Issue 1

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