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Table of Contents

Breaking Advances

Cancer Research 75th Anniversary Commentaries

Review

Integrated Systems and Technologies

  • Integrated Systems and Technologies
    Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer
    Zoe Hall, Zsuzsanna Ament, Catherine H. Wilson, Deborah L. Burkhart, Tom Ashmore, Albert Koulman, Trevor Littlewood, Gerard I. Evan and Julian L. Griffin
    Cancer Res August 15 2016 76 (16) 4608-4618; DOI:10.1158/0008-5472.CAN-15-3403

    These results show how MYC drives the production of specific eicosanoids critical for lung cancer cell survival and proliferation, with possible implications for the use of COX and LOX pathway inhibitors for lung cancer therapy.

  • Integrated Systems and Technologies
    Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines
    Sheng Guo, Wubin Qian, Jie Cai, Likun Zhang, Jean-Pierre Wery and Qi-Xiang Li
    Cancer Res August 15 2016 76 (16) 4619-4626; DOI:10.1158/0008-5472.CAN-15-3245

    This study describes a new method for cancer diagnosis based on molecular pathology, offering equivalence to histopathology as described for improved accuracy.

  • Integrated Systems and Technologies
    Design and Reporting of Targeted Anticancer Preclinical Studies: A Meta-Analysis of Animal Studies Investigating Sorafenib Antitumor Efficacy
    James Mattina, Nathalie MacKinnon, Valerie C. Henderson, Dean Fergusson and Jonathan Kimmelman
    Cancer Res August 15 2016 76 (16) 4627-4636; DOI:10.1158/0008-5472.CAN-15-3455

    Poor adherence to preclinical design and reporting guidelines, coupled with publication bias, threatens the reproducibility of preclinical research of candidate therapeutics, potentially overestimating their clinical utility.

  • Integrated Systems and Technologies
    Remodeling of the Epithelial–Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging
    Rahul Pal, Tuya Shilagard, Jinping Yang, Paula Villarreal, Tyra Brown, Suimin Qiu, Susan McCammon, Vicente Resto and Gracie Vargas
    Cancer Res August 15 2016 76 (16) 4637-4647; DOI:10.1158/0008-5472.CAN-16-0252

    Novel microscopic methods reveal topographical deformations in oral epithelial atypia that can distinguish precursor lesions from normal/benign mucosa.

Microenvironment and Immunology

  • Microenvironment and Immunology
    Follicular B Lymphomas Generate Regulatory T Cells via the ICOS/ICOSL Pathway and Are Susceptible to Treatment by Anti-ICOS/ICOSL Therapy
    Kieu-Suong Le, Marie-Laure Thibult, Sylvain Just-Landi, Sonia Pastor, Françoise Gondois-Rey, Samuel Granjeaud, Florence Broussais, Reda Bouabdallah, Renaud Colisson, Christophe Caux, Christine Ménétrier-Caux, Dominique Leroux, Luc Xerri and Daniel Olive
    Cancer Res August 15 2016 76 (16) 4648-4660; DOI:10.1158/0008-5472.CAN-15-0589

    ICOS+-activated Treg accumulate in follicular lymphoma tissues and inhibit not only conventional T cells but also follicular lymphoma B cells, suggesting that anti-ICOS immunotherapy could be efficacious in this disease setting.

  • Microenvironment and Immunology | AuthorChoice
    Therapeutic Efficacy of Cancer Stem Cell Vaccines in the Adjuvant Setting
    Yangyang Hu, Lin Lu, Yang Xia, Xin Chen, Alfred E. Chang, Robert E. Hollingsworth, Elaine Hurt, John Owen, Jeffrey S. Moyer, Mark E.P. Prince, Fu Dai, Yangyi Bao, Yi Wang, Joel Whitfield, Jian-Chuan Xia, Shiang Huang, Max S. Wicha and Qiao Li
    Cancer Res August 15 2016 76 (16) 4661-4672; DOI:10.1158/0008-5472.CAN-15-2664

    These findings offer a preclinical proof of concept for a more effective use of cancer stem-like cell–targeting dendritic cell vaccines in the adjuvant setting, that is, after excision of a primary tumor whose presence enforces immunosuppression.

  • Microenvironment and Immunology
    Checkpoint Antibodies but not T Cell–Recruiting Diabodies Effectively Synergize with TIL-Inducing γ-Irradiation
    Michael Hettich, Jayashree Lahoti, Shruthi Prasad and Gabriele Niedermann
    Cancer Res August 15 2016 76 (16) 4673-4683; DOI:10.1158/0008-5472.CAN-15-3451

    These findings suggest cautions in the use of T cell–recruiting bispecific antibodies for the treatment of solid tumors, but also reveal that immune checkpoint-blocking antibodies can synergize powerfully with radiation to cure even very large tumors.

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    Oncoprotein HBXIP Modulates Abnormal Lipid Metabolism and Growth of Breast Cancer Cells by Activating the LXRs/SREBP-1c/FAS Signaling Cascade
    Yu Zhao, Hang Li, Yingyi Zhang, Leilei Li, Runping Fang, Yinghui Li, Qian Liu, Weiying Zhang, Liyan Qiu, Fabao Liu, Xiaodong Zhang and Lihong Ye
    Cancer Res August 15 2016 76 (16) 4696-4707; DOI:10.1158/0008-5472.CAN-15-1734

    These findings elucidate how aberrant lipid metabolism pathways sustain breast cancer cell growth, deepening the evidence that targeting these pathways may be therapeutically useful.

  • Molecular and Cellular Pathobiology
    PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma
    Sameer Agnihotri, Brian Golbourn, Xi Huang, Marc Remke, Susan Younger, Rob A. Cairns, Alan Chalil, Christian A. Smith, Stacey-Lynn Krumholtz, Danielle Mackenzie, Patricia Rakopoulos, Vijay Ramaswamy, Michael S. Taccone, Paul S. Mischel, Gregory N. Fuller, Cynthia Hawkins, William L. Stanford, Michael D. Taylor, Gelareh Zadeh and James T. Rutka
    Cancer Res August 15 2016 76 (16) 4708-4719; DOI:10.1158/0008-5472.CAN-15-3079

    These findings offer a mechanistic rationale to attack aggressive brain cancers by reprogramming a critical metabolic pathway that sustains them.

  • Molecular and Cellular Pathobiology | AuthorChoice
    CSN1 Somatic Mutations in Penile Squamous Cell Carcinoma
    Andrew Feber, Daniel C. Worth, Ankur Chakravarthy, Patricia de Winter, Kunal Shah, Manit Arya, Muhammad Saqib, Raj Nigam, Peter R. Malone, Wei Shen Tan, Simon Rodney, Alex Freeman, Charles Jameson, Gareth A. Wilson, Tom Powles, Stephan Beck, Tim Fenton, Tyson V. Sharp, Asif Muneer and John D. Kelly
    Cancer Res August 15 2016 76 (16) 4720-4727; DOI:10.1158/0008-5472.CAN-15-3134

    This whole exome sequencing study of penile cancer, which is rare in developed countries but a significant burden in developing countries, offers the first comprehensive analysis of somatic genetic alterations in this malignancy.

  • Molecular and Cellular Pathobiology
    Tumor Suppressor HIPK2 Regulates Malignant Growth via Phosphorylation of Notch1
    Eun-Jung Ann, Mi-Yeon Kim, Ji-Hye Yoon, Ji-Seon Ahn, Eun-Hye Jo, Hye-Jin Lee, Hyun-Woo Lee, Hyeok-Gu Kang, Dong Wook Choi, Kyung-Hee Chun, Ji Shin Lee, Cheol Yong Choi, Adolfo A. Ferrando, Keesook Lee and Hee-Sae Park
    Cancer Res August 15 2016 76 (16) 4728-4740; DOI:10.1158/0008-5472.CAN-15-3310

    In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer.

  • Molecular and Cellular Pathobiology
    miR-196b Is Epigenetically Silenced during the Premalignant Stage of Lung Carcinogenesis
    Carmen S. Tellez, Daniel E. Juri, Kieu Do, Maria A. Picchi, Teresa Wang, Gang Liu, Avrum Spira and Steven A. Belinsky
    Cancer Res August 15 2016 76 (16) 4741-4751; DOI:10.1158/0008-5472.CAN-15-3367

    Targeted delivery of miR-196b, a tumor suppressor microRNA, may have preventive or therapeutic utility for the management of lung cancer.

  • Molecular and Cellular Pathobiology
    Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers
    Meghan Morrison Joly, Donna J. Hicks, Bayley Jones, Violeta Sanchez, Monica Valeria Estrada, Christian Young, Michelle Williams, Brent N. Rexer, Dos D. Sarbassov, William J. Muller, Dana Brantley-Sieders and Rebecca S. Cook
    Cancer Res August 15 2016 76 (16) 4752-4764; DOI:10.1158/0008-5472.CAN-15-3393

    mTORC2 inhibition may offer a promising therapeutic strategy to help eradicate HER2-amplified breast cancers, especially in those cases where Akt signaling is activated or tumors are resistant HER2 targeted therapy.

  • Molecular and Cellular Pathobiology | AuthorChoice
    Multiregion Whole-Exome Sequencing Uncovers the Genetic Evolution and Mutational Heterogeneity of Early-Stage Metastatic Melanoma
    Katja Harbst, Martin Lauss, Helena Cirenajwis, Karolin Isaksson, Frida Rosengren, Therese Törngren, Anders Kvist, Maria C. Johansson, Johan Vallon-Christersson, Bo Baldetorp, Åke Borg, Håkan Olsson, Christian Ingvar, Ana Carneiro and Göran Jönsson
    Cancer Res August 15 2016 76 (16) 4765-4774; DOI:10.1158/0008-5472.CAN-15-3476

    A multiregion sequencing approach reveals the diverse genetic events underlying intratumoral heterogeneity over the course of early metastatic melanoma, with possible implications for exploiting the mutational spectrum across multiple tumor specimens as a more reliable prognostic indicator.

  • Molecular and Cellular Pathobiology
    Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma
    Massimiliano Cadamuro, Gaia Spagnuolo, Luisa Sambado, Stefano Indraccolo, Giorgia Nardo, Antonio Rosato, Simone Brivio, Chiara Caslini, Tommaso Stecca, Marco Massani, Nicolò Bassi, Eugenio Novelli, Carlo Spirli, Luca Fabris and Mario Strazzabosco
    Cancer Res August 15 2016 76 (16) 4775-4784; DOI:10.1158/0008-5472.CAN-16-0188

    Low-dose chemotherapy may be more useful than traditional doses to block the metastatic progression of certain poorly managed tumors such as cholangiocarcinoma, an aggressive and poorly managed cancer of the liver bile duct.

Prevention and Epidemiology

  • Prevention and Epidemiology
    Cholesterol Metabolism and Prostate Cancer Lethality
    Konrad H. Stopsack, Travis A. Gerke, Jennifer A. Sinnott, Kathryn L. Penney, Svitlana Tyekucheva, Howard D. Sesso, Swen-Olof Andersson, Ove Andrén, James R. Cerhan, Edward L. Giovannucci, Lorelei A. Mucci and Jennifer R. Rider
    Cancer Res August 15 2016 76 (16) 4785-4790; DOI:10.1158/0008-5472.CAN-16-0903

    High intratumoral expression of squalene monooxygenase, the second rate-limiting enzyme of cholesterol synthesis, is found to be associated with a high risk of lethality in prostate cancer patients.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology
    Inhibiting DX2-p14/ARF Interaction Exerts Antitumor Effects in Lung Cancer and Delays Tumor Progression
    Ah-Young Oh, Youn Sang Jung, Jiseon Kim, Jee-Hyun Lee, Jung-Hyun Cho, Ho-Young Chun, Soyoung Park, Hyunchul Park, Sikeun Lim, Nam-Chul Ha, Jong Sook Park, Choon-Sik Park, Gyu-Yong Song and Bum-Joon Park
    Cancer Res August 15 2016 76 (16) 4791-4804; DOI:10.1158/0008-5472.CAN-15-1025

    These results suggest a new strategy to attenuate lung cancer progression by targeting the interaction of a new suppressor of p14/ARF function with potentially special relevance to treat cancers, which arise in heavy smokers.

  • Therapeutics, Targets, and Chemical Biology
    Novel Anticancer Agents Based on Targeting the Trimer Interface of the PRL Phosphatase
    Yunpeng Bai, Zhi-Hong Yu, Sijiu Liu, Lujuan Zhang, Ruo-Yu Zhang, Li-Fan Zeng, Sheng Zhang and Zhong-Yin Zhang
    Cancer Res August 15 2016 76 (16) 4805-4815; DOI:10.1158/0008-5472.CAN-15-2323

    These results offer a preclinical proof of concept for the use of small molecules that block trimerization of PRL phosphatases, a little explored class of important cancer target molecules.

  • Therapeutics, Targets, and Chemical Biology
    mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting by Antagonists of Oxidative Stress
    Jing Li, Sejeong Shin, Yang Sun, Sang-Oh Yoon, Chenggang Li, Erik Zhang, Jane Yu, Jianming Zhang and John Blenis
    Cancer Res August 15 2016 76 (16) 4816-4827; DOI:10.1158/0008-5472.CAN-15-2629

    These findings offer preclinical proof of concept for a combination strategy to selectively increase the cytotoxicity of mTORC1 inhibitors, which have performed poorly in clinic, based on cotargeting glutathione-controlled oxidative stress pathways.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis
    Julien A. Menard, Helena C. Christianson, Paulina Kucharzewska, Erika Bourseau-Guilmain, Katrin J. Svensson, Eva Lindqvist, Vineesh Indira Chandran, Lena Kjellén, Charlotte Welinder, Johan Bengzon, Maria C. Johansson and Mattias Belting
    Cancer Res August 15 2016 76 (16) 4828-4840; DOI:10.1158/0008-5472.CAN-15-2831

    This study unravels mechanisms of cancer cell adaptation to major stress factors of the tumor microenvironment associated with increased aggressiveness.

  • Therapeutics, Targets, and Chemical Biology
    Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia
    Lohith Bachegowda, Kerry Morrone, Shannon L. Winski, Ioannis Mantzaris, Matthias Bartenstein, Nandini Ramachandra, Orsi Giricz, Vineeth Sukrithan, George Nwankwo, Samira Shahnaz, Tushar D. Bhagat, Sanchari Bhattacharyya, Amer Assal, Aditi Shastri, Shanisha Gordon-Mitchell, Andrea Pellagatti, Jacqueline Boultwood, Carolina Schinke, Yiting Yu, Chandan Guha, James Rizzi, Jennifer Garrus, Suzy Brown, Lance Wollenberg, Grant Hogeland, Dale Wright, Mark Munson, Mareli Rodriguez, Stefan Gross, David Chantry, Yiyu Zou, Leonidas C. Platanias, Laurence E. Burgess, Kith Pradhan, Ulrich Steidl and Amit Verma
    Cancer Res August 15 2016 76 (16) 4841-4849; DOI:10.1158/0008-5472.CAN-15-3062

    These results provide preclinical proof of concept for an experimental drug that targets the key pathogenic contributions of angiopoietin-1 to the development of malignant stem-like myeloid cells.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies
    Timothy M. Shaver, Brian D. Lehmann, J. Scott Beeler, Chung-I Li, Zhu Li, Hailing Jin, Thomas P. Stricker, Yu Shyr and Jennifer A. Pietenpol
    Cancer Res August 15 2016 76 (16) 4850-4860; DOI:10.1158/0008-5472.CAN-16-0058

    This study highlights the importance of considering noncoding gene rearrangement fusions in cancer, along with the need to advance gene fusion detection technologies for characterizing the molecular features of heterogeneous cancers in this regard.

  • Therapeutics, Targets, and Chemical Biology
    Reduced Expression of Histone Methyltransferases KMT2C and KMT2D Correlates with Improved Outcome in Pancreatic Ductal Adenocarcinoma
    Joshua B.N. Dawkins, Jun Wang, Eleni Maniati, James A. Heward, Lola Koniali, Hemant M. Kocher, Sarah A. Martin, Claude Chelala, Frances R. Balkwill, Jude Fitzgibbon and Richard P. Grose
    Cancer Res August 15 2016 76 (16) 4861-4871; DOI:10.1158/0008-5472.CAN-16-0481

    These results highlight the importance of epigenetic modulation in pancreatic cancer, based on impact on patient survival, with possible implications for therapeutic management.

Tumor and Stem Cell Biology

Letters to the Editor

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Cancer Research: 76 (16)
August 2016
Volume 76, Issue 16

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