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Table of Contents

Breaking Advances

Reviews

Perspectives

Priority Report

  • Priority Report
    Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer
    Antti Ylipää, Kati Kivinummi, Annika Kohvakka, Matti Annala, Leena Latonen, Mauro Scaravilli, Kimmo Kartasalo, Simo-Pekka Leppänen, Serdar Karakurt, Janne Seppälä, Olli Yli-Harja, Teuvo L.J. Tammela, Wei Zhang, Tapio Visakorpi and Matti Nykter
    Cancer Res October 1 2015 75 (19) 4026-4031; DOI:10.1158/0008-5472.CAN-15-0217

    This first transcriptome sequencing of castration-resistant prostate cancer reports the discovery of an long noncoding RNA that may offer a druggable target in ERG+ prostate cancers.

Clinical Studies

  • Clinical Studies
    High-Resolution Rapid Diagnostic Imaging of Whole Prostate Biopsies Using Video-Rate Fluorescence Structured Illumination Microscopy
    Mei Wang, Hillary Z. Kimbrell, Andrew B. Sholl, David B. Tulman, Katherine N. Elfer, Tyler C. Schlichenmeyer, Benjamin R. Lee, Michelle Lacey and J. Quincy Brown
    Cancer Res October 1 2015 75 (19) 4032-4041; DOI:10.1158/0008-5472.CAN-14-3806

    This study describes the utility of a novel microscopic method for high-throughput, nondestructive pathologic imaging and diagnosis of malignant biopsy tissue, with the potential to replace current techniques and assess tissue quality and diagnosis at the point of acquisition.

Integrated Systems and Technologies

Microenvironment and Immunology

  • Microenvironment and Immunology | AuthorChoice
    Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages
    Casey Frankenberger, Daniel Rabe, Russell Bainer, Devipriya Sankarasharma, Kiran Chada, Thomas Krausz, Yoav Gilad, Lev Becker and Marsha Rich Rosner
    Cancer Res October 1 2015 75 (19) 4063-4073; DOI:10.1158/0008-5472.CAN-14-3394

    These findings suggest that ‘triple-negative’ breast cancer patients may benefit greatly from therapeutics that target tumor-associated macrophages, addressing a clinical need for effective targeted therapies in this setting.

  • Microenvironment and Immunology
    CD38-Expressing Myeloid-Derived Suppressor Cells Promote Tumor Growth in a Murine Model of Esophageal Cancer
    Tatiana A. Karakasheva, Todd J. Waldron, Evgeniy Eruslanov, Sang-Bae Kim, Ju-Seog Lee, Shaun O'Brien, Philip D. Hicks, Devraj Basu, Sunil Singhal, Fabio Malavasi and Anil K. Rustgi
    Cancer Res October 1 2015 75 (19) 4074-4085; DOI:10.1158/0008-5472.CAN-14-3639

    This report highlights CD38 as a new marker of highly immunosuppressive MDSC as well as a candidate therapeutic target, addressing a long-standing need to more fully define functional biomarkers in this key myeloid cell population mediating immune escape.

  • Microenvironment and Immunology | AuthorChoice
    Dll4 Blockade in Stromal Cells Mediates Antitumor Effects in Preclinical Models of Ovarian Cancer
    Frank Kuhnert, Guoying Chen, Sandra Coetzee, Nithya Thambi, Carlos Hickey, Jing Shan, Pavel Kovalenko, Irene Noguera-Troise, Eric Smith, Jeanette Fairhurst, Julian Andreev, Jessica R. Kirshner, Nicholas Papadopoulos and Gavin Thurston
    Cancer Res October 1 2015 75 (19) 4086-4096; DOI:10.1158/0008-5472.CAN-14-3773

    These findings establish a therapeutic rationale for antibody-based targeting of a Notch ligand in ovarian cancer, as an antiangiogenic strategy that is particularly potent in combination with VEGF blockade.

  • Microenvironment and Immunology
    Anti-CD20 Therapy Acts via FcγRIIIA to Diminish Responsiveness of Human Natural Killer Cells
    Cristina Capuano, Maddalena Romanelli, Chiara Pighi, Giuseppe Cimino, Angela Rago, Rosa Molfetta, Rossella Paolini, Angela Santoni and Ricciarda Galandrini
    Cancer Res October 1 2015 75 (19) 4097-4108; DOI:10.1158/0008-5472.CAN-15-0781

    These findings define a novel mechanism of immune exhaustion caused by rituximab or related CD20 mAb in human natural killer cells, with potentially negative implications for patients treated with these therapies.

  • Microenvironment and Immunology
    Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors
    Ferdia A. Gallagher, Helen Sladen, Mikko I. Kettunen, Eva M. Serrao, Tiago B. Rodrigues, Alan Wright, Andrew B. Gill, Sarah McGuire, Thomas C. Booth, Joan Boren, Alan McIntyre, Jodi L. Miller, Shen-Han Lee, Davina Honess, Sam E. Day, De-En Hu, William J. Howat, Adrian L. Harris and Kevin M. Brindle
    Cancer Res October 1 2015 75 (19) 4109-4118; DOI:10.1158/0008-5472.CAN-15-0857

    An enzyme that is highly elevated in hypoxic conditions and that engenders metastatic progression is found to have a critical role for lowering extracellular pH, with potential implications as a therapeutic target in hypoxic conditions when tumors are typically resistant to therapy.

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells during Carcinogenesis
    Garcilaso Riesco-Eizaguirre, León Wert-Lamas, Javier Perales-Patón, Ana Sastre-Perona, Lara P. Fernández and Pilar Santisteban
    Cancer Res October 1 2015 75 (19) 4119-4130; DOI:10.1158/0008-5472.CAN-14-3547

    These findings reveal that a microRNA network underlies thyroid cell differentiation and function, with important implications for overcoming treatment-refractory metastatic thyroid cancer.

  • Molecular and Cellular Pathobiology
    Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma
    Liem M. Phan, Enrique Fuentes-Mattei, Weixin Wu, Guermarie Velazquez-Torres, Kanishka Sircar, Christopher G. Wood, Tao Hai, Camilo Jimenez, Gilbert J. Cote, Levent Ozsari, Marie-Claude Hofmann, Siyuan Zheng, Roeland Verhaak, Lance Pagliaro, Maria Angelica Cortez, Mong-Hong Lee, Sai-Ching J. Yeung and Mouhammed Amir Habra
    Cancer Res October 1 2015 75 (19) 4131-4142; DOI:10.1158/0008-5472.CAN-14-3707

    These findings show that HGF/MET signaling enhances cancer hallmarks in adrenocortical carcinoma, where it may also contribute to drug resistance, with implications for the use of MET inhibitors as a clinical treatment strategy in this disease.

  • Molecular and Cellular Pathobiology
    Enhanced Chemokine Receptor Recycling and Impaired S1P1 Expression Promote Leukemic Cell Infiltration of Lymph Nodes in Chronic Lymphocytic Leukemia
    Laura Patrussi, Nagaja Capitani, Veronica Martini, Marco Pizzi, Valentina Trimarco, Federica Frezzato, Filippo Marino, Gianpietro Semenzato, Livio Trentin and Cosima T. Baldari
    Cancer Res October 1 2015 75 (19) 4153-4163; DOI:10.1158/0008-5472.CAN-15-0986

    These findings show how cell surface recycling dynamics controlled by endocytotic processes account for high surface levels of CXCR4 and CCR7 in chronic B cell tumors, and how the targeted drug ibrutinib impacts this balance in achieving therapeutic responses.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology
    VR23: A Quinoline–Sulfonyl Hybrid Proteasome Inhibitor That Selectively Kills Cancer via Cyclin E–Mediated Centrosome Amplification
    Sheetal Pundir, Hai-Yen Vu, V. Raja Solomon, Rebecca McClure and Hoyun Lee
    Cancer Res October 1 2015 75 (19) 4164-4175; DOI:10.1158/0008-5472.CAN-14-3370

    These results identify a structurally novel proteasome inhibitor with uniquely selective anticancer properties and other desirable features, providing a preclinical proof of concept that encourages further clinical development.

  • Therapeutics, Targets, and Chemical Biology
    Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II Poisons in Cancer
    Ruud H. Wijdeven, Baoxu Pang, Sabina Y. van der Zanden, Xiaohang Qiao, Vincent Blomen, Marlous Hoogstraat, Esther H. Lips, Lennert Janssen, Lodewyk Wessels, Thijn R. Brummelkamp and Jacques Neefjes
    Cancer Res October 1 2015 75 (19) 4176-4187; DOI:10.1158/0008-5472.CAN-15-0380

    These findings describe the characterization of three novel mechanisms underlying resistance to the commonly used anticancer drugs doxorubicin and etoposide, with implications for stratifying cancer patients into the most effective treatment regimens.

  • Therapeutics, Targets, and Chemical Biology
    Akt Kinase-Interacting Protein 1 Signals through CREB to Drive Diffuse Malignant Mesothelioma
    Tadaaki Yamada, Joseph M. Amann, Koji Fukuda, Shinji Takeuchi, Naoya Fujita, Hisanori Uehara, Shotaro Iwakiri, Kazumi Itoi, Konstantin Shilo, Seiji Yano and David P. Carbone
    Cancer Res October 1 2015 75 (19) 4188-4197; DOI:10.1158/0008-5472.CAN-15-0858

    These findings suggest an important role for the Aki1/CREB axis in the pathogenesis of diffuse malignant mesothelioma, a deadly lung cancer, and also offer a preclinical rationale to target Aki1 in this disease setting.

  • Therapeutics, Targets, and Chemical Biology
    Feed-Forward Reciprocal Activation of PAFR and STAT3 Regulates Epithelial–Mesenchymal Transition in Non–Small Cell Lung Cancer
    Jie Chen, Tian Lan, Weimin Zhang, Lijia Dong, Nan Kang, Shumin Zhang, Ming Fu, Bing Liu, Kangtai Liu and Qimin Zhan
    Cancer Res October 1 2015 75 (19) 4198-4210; DOI:10.1158/0008-5472.CAN-15-1062

    These results elucidate a powerful mechanism of self-reinforcing malignant character in lung adenocarcinoma, driven by a tripartite G protein-coupled receptor that may offer an appealing therapeutic target.

  • Therapeutics, Targets, and Chemical Biology
    Identification of P450 Oxidoreductase as a Major Determinant of Sensitivity to Hypoxia-Activated Prodrugs
    Francis W. Hunter, Richard J. Young, Zvi Shalev, Ravi N. Vellanki, Jingli Wang, Yongchuan Gu, Naveen Joshi, Sreevalsan Sreebhavan, Ilan Weinreb, David P. Goldstein, Jason Moffat, Troy Ketela, Kevin R. Brown, Marianne Koritzinsky, Benjamin Solomon, Danny Rischin, William R. Wilson and Bradly G. Wouters
    Cancer Res October 1 2015 75 (19) 4211-4223; DOI:10.1158/0008-5472.CAN-15-1107

    This study identifies a factor that appears to be critical for the response to a class of hypoxia-targeting drugs, with implications for improving the treatment of hypoxic solid tumors.

Tumor and Stem Cell Biology

  • Tumor and Stem Cell Biology
    Ceacam1L Modulates STAT3 Signaling to Control the Proliferation of Glioblastoma-Initiating Cells
    Sadahiro Kaneko, Yuka Nakatani, Tatsuya Takezaki, Takuichiro Hide, Daisuke Yamashita, Naoki Ohtsu, Takanori Ohnishi, Shunsuke Terasaka, Kiyohiro Houkin and Toru Kondo
    Cancer Res October 1 2015 75 (19) 4224-4234; DOI:10.1158/0008-5472.CAN-15-0412

    These results identify a role for a proangiogenic immunosuppressive cell adhesion protein in maintaining cancer stem-like cell functions in the most commonly deadly brain tumor.

  • Tumor and Stem Cell Biology
    Colon Cancer Growth and Dissemination Relies upon Thrombin, Stromal PAR-1, and Fibrinogen
    Gregory N. Adams, Leah Rosenfeldt, Malinda Frederick, Whitney Miller, Dusty Waltz, Keith Kombrinck, Kathryn E. McElhinney, Matthew J. Flick, Brett P. Monia, Alexey S. Revenko and Joseph S. Palumbo
    Cancer Res October 1 2015 75 (19) 4235-4243; DOI:10.1158/0008-5472.CAN-15-0964

    Colon cancers may exhibit a special reliance on hemostatic factors such as thrombin, which appears to act as a multifaceted positive modifier of primary tumor growth, invasion, and metastasis, with immediate therapeutic implications for the clinical exploration of inhibitors of thrombin or thrombin generation in this disease setting.

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Cancer Research: 75 (19)
October 2015
Volume 75, Issue 19

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