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Table of Contents

Breaking Advances

Reviews

Priority Reports

  • Priority Reports | AuthorChoice
    A Genetic Mouse Model of Invasive Endometrial Cancer Driven by Concurrent Loss of Pten and Lkb1 Is Highly Responsive to mTOR Inhibition
    Hailing Cheng, Pixu Liu, Fan Zhang, Erbo Xu, Lynn Symonds, Carolynn E. Ohlson, Roderick T. Bronson, Sauveur-Michel Maira, Emmanuelle Di Tomaso, Jane Li, Andrea P. Myers, Lewis C. Cantley, Gordon B. Mills and Jean J. Zhao
    Cancer Res January 1 2014 74 (1) 15-23; DOI:10.1158/0008-5472.CAN-13-0544

    These findings suggest insights into the basis for development of an aggressive form of endometrial cancer that is driven by deregulated mTOR signaling.

  • Priority Reports
    Tumor Hypoxia Does Not Drive Differentiation of Tumor-Associated Macrophages but Rather Fine-Tunes the M2-like Macrophage Population
    Damya Laoui, Eva Van Overmeire, Giusy Di Conza, Chiara Aldeni, Jiri Keirsse, Yannick Morias, Kiavash Movahedi, Isabelle Houbracken, Elio Schouppe, Yvon Elkrim, Oussama Karroum, Bénédicte Jordan, Peter Carmeliet, Conny Gysemans, Patrick De Baetselier, Massimiliano Mazzone and Jo A. Van Ginderachter
    Cancer Res January 1 2014 74 (1) 24-30; DOI:10.1158/0008-5472.CAN-13-1196

    This study challenges the notion that TAMs are a primary beneficiary of hypoxia in the tumor microenvironment, shifting attention to M2 macrophages to explain how the poorly organized vasculature of tumors promotes malignant progression.

  • Priority Reports
    Targeting PARP-1 Allosteric Regulation Offers Therapeutic Potential against Cancer
    Jamin D. Steffen, Renee M. Tholey, Marie-France Langelier, Jamie L. Planck, Matthew J. Schiewer, Shruti Lal, Nikolai A. Bildzukewicz, Charles J. Yeo, Karen E. Knudsen, Jonathan R. Brody and John M. Pascal
    Cancer Res January 1 2014 74 (1) 31-37; DOI:10.1158/0008-5472.CAN-13-1701

    This study establishes a new strategy to selectively inhibit the DNA repair enzyme PARP-1, a clinically validated target for cancer treatment.

  • Priority Reports
    The NADH Oxidase ENOX1, a Critical Mediator of Endothelial Cell Radiosensitization, Is Crucial for Vascular Development
    Amudhan Venkateswaran, Konjeti R. Sekhar, Daniel S. Levic, David B. Melville, Travis A. Clark, Witold M. Rybski, Alexandra J. Walsh, Melissa C. Skala, Peter A. Crooks, Ela W. Knapik and Michael L. Freeman
    Cancer Res January 1 2014 74 (1) 38-43; DOI:10.1158/0008-5472.CAN-13-1981

    ENOX1 may offer an appealing new antiangiogenic target for cancer therapy based on its role in influencing sensitivity to radiotherapy and DNA-damaging cytotoxic agents.

Integrated Systems and Technologies

  • Integrated Systems and Technologies
    A Macrophage-Specific Fluorescent Probe for Intraoperative Lymph Node Staging
    Jung Sun Yoo, Sung-Chan Lee, Zhi Yen Jow, Pamela Yun Xiang Koh and Young-Tae Chang
    Cancer Res January 1 2014 74 (1) 44-55; DOI:10.1158/0008-5472.CAN-13-2129

    These findings illustrate an intraoperative platform technology to improve lymph node staging, providing fluorescent guidance during cancer surgery that might reduce complications such as lymphedema.

  • Integrated Systems and Technologies
    A Preclinical Assay for Chemosensitivity in Multiple Myeloma
    Zayar P. Khin, Maria L.C. Ribeiro, Timothy Jacobson, Lori Hazlehurst, Lia Perez, Rachid Baz, Kenneth Shain and Ariosto S. Silva
    Cancer Res January 1 2014 74 (1) 56-67; DOI:10.1158/0008-5472.CAN-13-2397

    This study describes a system to test cancer cells from patients against a panel of drugs and to generate computational models with the potential to inform the best treatment for individual patients.

Microenvironment and Immunology

  • Microenvironment and Immunology
    Regulation of CD4+NKG2D+ Th1 Cells in Patients with Metastatic Melanoma Treated with Sorafenib: Role of IL-15Rα and NKG2D Triggering
    Ana I. Romero, Nathalie Chaput, Vichnou Poirier-Colame, Sylvie Rusakiewicz, Nicolas Jacquelot, Kariman Chaba, Erwan Mortier, Yannick Jacques, Sophie Caillat-Zucman, Caroline Flament, Anne Caignard, Meriem Messaoudene, Anne Aupérin, Philippe Vielh, Philippe Dessen, Camillo Porta, Christine Mateus, Maha Ayyoub, Danila Valmori, Alexander Eggermont, Caroline Robert and Laurence Zitvogel
    Cancer Res January 1 2014 74 (1) 68-80; DOI:10.1158/0008-5472.CAN-13-1186

    These important findings suggest that the multikinase inhibitor sorafenib acts as an immunotherapy to modulate T cells in the cancer patient, inducing a rare but clinically important subset of T cells that has been associated with prolonged survival in metastatic melanoma patients.

  • Microenvironment and Immunology
    Mature Cytotoxic CD56bright/CD16+ Natural Killer Cells Can Infiltrate Lymph Nodes Adjacent to Metastatic Melanoma
    Meriem Messaoudene, Giulia Fregni, Emmanuelle Fourmentraux-Neves, Johan Chanal, Eve Maubec, Sarra Mazouz-Dorval, Benoit Couturaud, Angelique Girod, Xavier Sastre-Garau, Sebastien Albert, Charles Guédon, Lydia Deschamps, Delphine Mitilian, Isabelle Cremer, Nicolas Jacquelot, Sylvie Rusakiewicz, Laurence Zitvogel, Marie-Francoise Avril and Anne Caignard
    Cancer Res January 1 2014 74 (1) 81-92; DOI:10.1158/0008-5472.CAN-13-1303

    Metastatic lymph nodes from melanoma patients contain a unique subset of natural killer cells endowed with high cytotoxic potential toward melanoma cells, the activation of which can be realized by exposure to IL-2 or IL-15.

  • Microenvironment and Immunology
    T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing
    Ko Kudo, Chihaya Imai, Paolo Lorenzini, Takahiro Kamiya, Koji Kono, Andrew M. Davidoff, Wee Joo Chng and Dario Campana
    Cancer Res January 1 2014 74 (1) 93-103; DOI:10.1158/0008-5472.CAN-13-1365

    This report describes a means to endow T lymphocytes with antibody-dependent cell cytotoxicity, offering a powerful strategy to improve antibody-based immunotherapies for human cancer.

  • Microenvironment and Immunology
    Doxorubicin Eliminates Myeloid-Derived Suppressor Cells and Enhances the Efficacy of Adoptive T-Cell Transfer in Breast Cancer
    Darya Alizadeh, Malika Trad, Neale T. Hanke, Claire B. Larmonier, Nona Janikashvili, Bernard Bonnotte, Emmanuel Katsanis and Nicolas Larmonier
    Cancer Res January 1 2014 74 (1) 104-118; DOI:10.1158/0008-5472.CAN-13-1545

    This study shows how a traditional cytotoxic cancer drug can be used to reverse myeloid immunosuppression in the tumor microenvironment and to enhance the efficacy of adoptively transferred T cells that attack tumors, creating a highly effective immunochemotherapy regimen.

  • Microenvironment and Immunology
    Cytokine-Induced Killer Cells Eradicate Bone and Soft-Tissue Sarcomas
    Dario Sangiolo, Giulia Mesiano, Loretta Gammaitoni, Valeria Leuci, Maja Todorovic, Lidia Giraudo, Cristina Cammarata, Carmine Dell'Aglio, Lorenzo D'Ambrosio, Alberto Pisacane, Ivana Sarotto, Sara Miano, Ivana Ferrero, Fabrizio Carnevale-Schianca, Ymera Pignochino, Francesco Sassi, Andrea Bertotti, Wanda Piacibello, Franca Fagioli, Massimo Aglietta and Giovanni Grignani
    Cancer Res January 1 2014 74 (1) 119-129; DOI:10.1158/0008-5472.CAN-13-1559

    This report offers a preclinical proof-of-concept for a novel type of cellular immunotherapy to attack untreatable metastatic sarcomas, which continue to pose a major clinical challenge.

  • Microenvironment and Immunology | AuthorChoice
    Transcriptional Profiling of Melanoma Sentinel Nodes Identify Patients with Poor Outcome and Reveal an Association of CD30+ T Lymphocytes with Progression
    Viviana Vallacchi, Elisabetta Vergani, Chiara Camisaschi, Paola Deho, Antonello D. Cabras, Marialuisa Sensi, Loris De Cecco, Niccolò Bassani, Federico Ambrogi, Antonino Carbone, Federica Crippa, Barbara Vergani, Paola Frati, Flavio Arienti, Roberto Patuzzo, Antonello Villa, Elia Biganzoli, Silvana Canevari, Mario Santinami, Chiara Castelli, Licia Rivoltini and Monica Rodolfo
    Cancer Res January 1 2014 74 (1) 130-140; DOI:10.1158/0008-5472.CAN-13-1672

    By deepening the evidence that sentinel lymph nodes help direct tumoral immunosuppression, this study identifies an immune activation marker associated with poor prognosis that might allow targeting by a drug recently approved by the FDA.

  • Microenvironment and Immunology
    Effects of Notch Signaling on Regulation of Myeloid Cell Differentiation in Cancer
    Pingyan Cheng, Vinit Kumar, Hao Liu, Je-In Youn, Mayer Fishman, Simon Sherman and Dmitry Gabrilovich
    Cancer Res January 1 2014 74 (1) 141-152; DOI:10.1158/0008-5472.CAN-13-1686

    These results suggest new insights into how abnormal myeloid cells accumulate in tumors, with possible implications for therapy of cancers driven by Notch.

  • Microenvironment and Immunology | AuthorChoice
    Inhibition of CSF-1 Receptor Improves the Antitumor Efficacy of Adoptive Cell Transfer Immunotherapy
    Stephen Mok, Richard C. Koya, Christopher Tsui, Jingying Xu, Lídia Robert, Lily Wu, Thomas G. Graeber, Brian L. West, Gideon Bollag and Antoni Ribas
    Cancer Res January 1 2014 74 (1) 153-161; DOI:10.1158/0008-5472.CAN-13-1816

    These findings suggest an important new use for inhibitors of a myeloid cell receptor that is responsible for recruiting immune-suppressive cells into tumors as a strategy to enhance adoptive T-cell immunotherapy.

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer
    Adam J. MacNeil, Shun-Chang Jiao, Lori A. McEachern, Yong Jun Yang, Amanda Dennis, Haiming Yu, Zhaolin Xu, Jean S. Marshall and Tong-Jun Lin
    Cancer Res January 1 2014 74 (1) 162-172; DOI:10.1158/0008-5472.CAN-13-1310

    These findings reveal the functional significance of a MAPK kinase as a tumor suppressor in breast cancer, improving understanding of the dynamic role of the MAPK pathway in tumor progression.

  • Molecular and Cellular Pathobiology
    Integrin-Free Tetraspanin CD151 Can Inhibit Tumor Cell Motility upon Clustering and Is a Clinical Indicator of Prostate Cancer Progression
    Trenis D. Palmer, Carlos H. Martínez, Catalina Vasquez, Katie E. Hebron, Celestial Jones-Paris, Shanna A. Arnold, Susanne M. Chan, Venu Chalasani, Jose A. Gomez-Lemus, Andrew K. Williams, Joseph L. Chin, Giovanna A. Giannico, Tatiana Ketova, John D. Lewis and Andries Zijlstra
    Cancer Res January 1 2014 74 (1) 173-187; DOI:10.1158/0008-5472.CAN-13-0275

    A common component of cell surface scaffolds that organize cell motility and physiology is altered during oncogenesis in a manner that confers cancer cells with aggressive qualities, causing poor outcomes.

  • Molecular and Cellular Pathobiology
    Casein Kinase 1ε Promotes Cell Proliferation by Regulating mRNA Translation
    Sejeong Shin, Laura Wolgamott, Philippe P. Roux and Sang-Oh Yoon
    Cancer Res January 1 2014 74 (1) 201-211; DOI:10.1158/0008-5472.CAN-13-1175

    These findings suggest a rationale for a generalized strategy to treat human cancers by blocking a pivotal kinase-regulated step in mRNA translation.

  • Molecular and Cellular Pathobiology
    Bcl2 Induces DNA Replication Stress by Inhibiting Ribonucleotide Reductase
    Maohua Xie, Yun Yen, Taofeek K. Owonikoko, Suresh S. Ramalingam, Fadlo R. Khuri, Walter J. Curran, Paul W. Doetsch and Xingming Deng
    Cancer Res January 1 2014 74 (1) 212-223; DOI:10.1158/0008-5472.CAN-13-1536-T

    These findings uncover a novel link between Bcl2 function and the progress of DNA replication, with potential implications on how to apply Bcl2 inhibitors in the clinic for cancer treatment.

  • Molecular and Cellular Pathobiology | AuthorChoice
    3′-UTR Poly(T/U) Tract Deletions and Altered Expression of EWSR1 Are a Hallmark of Mismatch Repair–Deficient Cancers
    Shivendra Kishore, Salvatore Piscuoglio, Michal B. Kovac, Annette Gylling, Friedel Wenzel, Francesca Trapani, Hans Joerg Altermatt, Valentina Mele, Giancarlo Marra, Päivi Peltomäki, Luigi Terracciano, Mihaela Zavolan and Karl Heinimann
    Cancer Res January 1 2014 74 (1) 224-234; DOI:10.1158/0008-5472.CAN-13-2100

    This study identifies a novel genetic locus that is fully informative and accurate in detecting mismatch-repair deficient cancers, with major implications for routine daily practice in the clinic.

Prevention and Epidemiology

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology
    MET and AXL Inhibitor NPS-1034 Exerts Efficacy against Lung Cancer Cells Resistant to EGFR Kinase Inhibitors Because of MET or AXL Activation
    Jin Kyung Rho, Yun Jung Choi, Seon Ye Kim, Tae Won Kim, Eun Kyung Choi, Seon-Joo Yoon, Bu Man Park, Eunhye Park, Jong Hwan Bae, Chang-Min Choi and Jae Cheol Lee
    Cancer Res January 1 2014 74 (1) 253-262; DOI:10.1158/0008-5472.CAN-13-1103

    A new drug that targets two tyrosine kinase receptors that drive invasive growth and drug resistance may be particularly useful for treatment of acquired resistance to EGFR inhibitors.

  • Therapeutics, Targets, and Chemical Biology
    A Reevaluation of CD22 Expression in Human Lung Cancer
    Laurentiu M. Pop, Stephen Barman, Chunli Shao, Jonathan C. Poe, Guglielmo M. Venturi, John M. Shelton, Iliodora V. Pop, David E. Gerber, Luc Girard, Xiao-yun Liu, Carmen Behrens, Jaime Rodriguez-Canales, Hui Liu, Ignacio I. Wistuba, James A. Richardson, John D. Minna, Thomas F. Tedder and Ellen S. Vitetta
    Cancer Res January 1 2014 74 (1) 263-271; DOI:10.1158/0008-5472.CAN-13-1436

    These findings challenge a previous study reporting widespread overexpression of the cell surface protein CD22 in lung cancers, for which it had been suggested as a new target for immunotherapy.

  • Therapeutics, Targets, and Chemical Biology
    USP22 Regulates Oncogenic Signaling Pathways to Drive Lethal Cancer Progression
    Randy S. Schrecengost, Jeffry L. Dean, Jonathan F. Goodwin, Matthew J. Schiewer, Mark W. Urban, Timothy J. Stanek, Robyn T. Sussman, Jessica L. Hicks, Ruth C. Birbe, Rossitza A. Draganova-Tacheva, Tapio Visakorpi, Angelo M. DeMarzo, Steven B. McMahon and Karen E. Knudsen
    Cancer Res January 1 2014 74 (1) 272-286; DOI:10.1158/0008-5472.CAN-13-1954

    These findings define a deubiquitinating enzyme as an important positive modifier of tumor progression, providing a strong rationale for it as an appealing therapeutic target to treat advanced cancers.

  • Therapeutics, Targets, and Chemical Biology | Free Article
    Genome-wide Profiling of Genetic Synthetic Lethality Identifies CDK12 as a Novel Determinant of PARP1/2 Inhibitor Sensitivity
    Ilirjana Bajrami, Jessica R. Frankum, Asha Konde, Rowan E. Miller, Farah L. Rehman, Rachel Brough, James Campbell, David Sims, Rumana Rafiq, Sean Hooper, Lina Chen, Iwanka Kozarewa, Ioannis Assiotis, Kerry Fenwick, Rachael Natrajan, Christopher J. Lord and Alan Ashworth
    Cancer Res January 1 2014 74 (1) 287-297; DOI:10.1158/0008-5472.CAN-13-2541

    These important findings suggest much greater utility for cancer treatment with PARP inhibitors than appreciated previously and also reveal a clinically relevant biomarker that is likely to be important for predicting PARP inhibitor responses.

  • Therapeutics, Targets, and Chemical Biology
    SIRT1 and AMPK Mediate Hypoxia-Induced Resistance of Non–Small Cell Lung Cancers to Cisplatin and Doxorubicin
    Dong Hoon Shin, Yong-Joon Choi and Jong-Wan Park
    Cancer Res January 1 2014 74 (1) 298-308; DOI:10.1158/0008-5472.CAN-13-2620

    This study provides a preclinical proof-of-concept to target the SIRT1–AMPK pathway as a strategy to overcome hypoxia-induced chemoresistance in lung cancer, with potentially broader implications for solid tumors generally.

Tumor and Stem Cell Biology

  • Tumor and Stem Cell Biology
    ERK1/2 Blockade Prevents Epithelial–Mesenchymal Transition in Lung Cancer Cells and Promotes Their Sensitivity to EGFR Inhibition
    Janine M. Buonato and Matthew J. Lazzara
    Cancer Res January 1 2014 74 (1) 309-319; DOI:10.1158/0008-5472.CAN-12-4721

    Combining targeted inhibitors of MEK or ERK with EGFR inhibitors not only restrains the epithelial–mesenchymal transition in lung cancer cells associated with drug resistance but also overcomes the resistance to EGFR-targeted therapy, suggesting immediate applications in the clinic, where this issue is both timely and important.

  • Tumor and Stem Cell Biology | AuthorChoice
    ΔNp63 Promotes Pediatric Neuroblastoma and Osteosarcoma by Regulating Tumor Angiogenesis
    Hemant K. Bid, Ryan D. Roberts, Maren Cam, Anthony Audino, Raushan T. Kurmasheva, Jiayuh Lin, Peter J. Houghton and Hakan Cam
    Cancer Res January 1 2014 74 (1) 320-329; DOI:10.1158/0008-5472.CAN-13-0894

    These findings reveal a key support to tumor angiogenesis in two aggressive childhood cancers, with implications for understanding progression and potential treatments.

  • Tumor and Stem Cell Biology
    Cancer Usurps Skeletal Muscle as an Energy Repository
    Yi Luo, Junya Yoneda, Hitoshi Ohmori, Takamitsu Sasaki, Kazutaka Shimbo, Sachise Eto, Yumiko Kato, Hiroshi Miyano, Tsuyoshi Kobayashi, Tomonori Sasahira, Yoshitomo Chihara and Hiroki Kuniyasu
    Cancer Res January 1 2014 74 (1) 330-340; DOI:10.1158/0008-5472.CAN-13-1052

    This important study shows how budding tumors recruit muscle to supply glutamine to cancer cells as an energy source through the release of HMGB1, a proinflammatory autophagy-inducing molecule that influences muscle physiology.

  • Tumor and Stem Cell Biology
    Neuregulin Autocrine Signaling Promotes Self-Renewal of Breast Tumor-Initiating Cells by Triggering HER2/HER3 Activation
    Cleo Yi-Fang Lee, Yuan Lin, Scott V. Bratman, Weiguo Feng, Angera H. Kuo, Ferenc A. Scheeren, Jesse M. Engreitz, Sushama Varma, Robert B. West and Maximilian Diehn
    Cancer Res January 1 2014 74 (1) 341-352; DOI:10.1158/0008-5472.CAN-13-1055

    This important work shows why HER2-targeting therapies might benefit a considerably larger number of breast cancer patients than they currently reach.

  • Tumor and Stem Cell Biology
    Tumor Suppressor NF2/Merlin Is a Microtubule Stabilizer
    Zlatko Smole, Claudio R. Thoma, Kathryn T. Applegate, Maria Duda, Katrin L. Gutbrodt, Gaudenz Danuser and Wilhelm Krek
    Cancer Res January 1 2014 74 (1) 353-362; DOI:10.1158/0008-5472.CAN-13-1334

    NF2 regulates the dynamic instability of microtubules, a function shared with the tumor suppressor VHL that also helps block aberrant microtubule-mediated processes needed for tumorigenesis.

  • Tumor and Stem Cell Biology
    14-3-3ζ Orchestrates Mammary Tumor Onset and Progression via miR-221–Mediated Cell Proliferation
    Sumaiyah K. Rehman, Shau-Hsuan Li, Shannon L. Wyszomierski, Qingfei Wang, Ping Li, Ozgur Sahin, Yi Xiao, Siyuan Zhang, Yan Xiong, Jun Yang, Hai Wang, Hua Guo, Jitao D. Zhang, Daniel Medina, William J. Muller and Dihua Yu
    Cancer Res January 1 2014 74 (1) 363-373; DOI:10.1158/0008-5472.CAN-13-2016

    This study establishes a powerful oncogenic function for a factor with a broad-acting modifier role in signaling that is commonly overexpressed in breast cancer cells, with potential implications for etiology, diagnosis, and prognosis.

  • Tumor and Stem Cell Biology
    Activation of the FGFR–STAT3 Pathway in Breast Cancer Cells Induces a Hyaluronan-Rich Microenvironment That Licenses Tumor Formation
    Laura R. Bohrer, Pavlina Chuntova, Lindsey K. Bade, Thomas C. Beadnell, Ronald P. Leon, Nicholas J. Brady, Yungil Ryu, Jodi E. Goldberg, Stephen C. Schmechel, Joseph S. Koopmeiners, James B. McCarthy and Kathryn L. Schwertfeger
    Cancer Res January 1 2014 74 (1) 374-386; DOI:10.1158/0008-5472.CAN-13-2469

    Aberrant growth factor receptor signaling in tumor cells leads to profound changes in their microenvironment that can promote therapeutic resistance and posttreatment relapses.

  • Tumor and Stem Cell Biology | AuthorChoice
    Proteogenomic Analysis Reveals Unanticipated Adaptations of Colorectal Tumor Cells to Deficiencies in DNA Mismatch Repair
    Patrick J. Halvey, Xiaojing Wang, Jing Wang, Ajaz A. Bhat, Punita Dhawan, Ming Li, Bing Zhang, Daniel C. Liebler and Robbert J.C. Slebos
    Cancer Res January 1 2014 74 (1) 387-397; DOI:10.1158/0008-5472.CAN-13-2488

    Global proteomic profiling reveals adaptations to mutations in DNA mismatch repair that occur in certain colon cancers that were not previously appreciated, providing a broader basis to mechanistically interpret phenotypes seen in colon cancer patients.

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Cancer Research: 74 (1)
January 2014
Volume 74, Issue 1

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