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Table of Contents

Breaking Advances

Reviews

Microenvironment and Immunology

  • Microenvironment and Immunology
    Breast Cancer Cell–Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes
    Cristina Ghirelli, Fabien Reyal, Marine Jeanmougin, Raphaël Zollinger, Philémon Sirven, Paula Michea, Christophe Caux, Nathalie Bendriss-Vermare, Marie-Hélène Donnadieu, Martial Caly, Virginie Fourchotte, Anne Vincent-Salomon, Brigitte Sigal-Zafrani, Xavier Sastre-Garau and Vassili Soumelis
    Cancer Res July 15 2015 75 (14) 2775-2787; DOI:10.1158/0008-5472.CAN-14-2386

    This study describes a mechanism through which an aggressive breast cancer activates pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to malignancy.

  • Microenvironment and Immunology | AuthorChoice
    NOS Inhibition Modulates Immune Polarization and Improves Radiation-Induced Tumor Growth Delay
    Lisa A. Ridnour, Robert Y.S. Cheng, Jonathan M. Weiss, Sukhbir Kaur, David R. Soto-Pantoja, Debashree Basudhar, Julie L. Heinecke, C. Andrew Stewart, William DeGraff, Anastasia L. Sowers, Angela Thetford, Aparna H. Kesarwala, David D. Roberts, Howard A. Young, James B. Mitchell, Giorgio Trinchieri, Robert H. Wiltrout and David A. Wink
    Cancer Res July 15 2015 75 (14) 2788-2799; DOI:10.1158/0008-5472.CAN-14-3011

    NOS inhibition has long been studied in cancer to limited impact, but these new preclinical results show how inhibiting NOS in patients after they undergo radiotherapy can relieve immune escape in the tumor microenvironment and greatly improve treatment responses.

  • Microenvironment and Immunology
    Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells
    Albert Lo, Liang-Chuan S. Wang, John Scholler, James Monslow, Diana Avery, Kheng Newick, Shaun O'Brien, Rebecca A. Evans, David J. Bajor, Cynthia Clendenin, Amy C. Durham, Elizabeth L. Buza, Robert H. Vonderheide, Carl H. June, Steven M. Albelda and Ellen Puré
    Cancer Res July 15 2015 75 (14) 2800-2810; DOI:10.1158/0008-5472.CAN-14-3041

    This report identifies a stromal cell population expressing the fibroblast activation protein (FAP), which is required for the desmoplastic response seen in many human carcinomas, also showing how FAP-expressing cells promote tumor growth via immune suppression and immune-independent remodeling of the stromal microenvironment.

  • Microenvironment and Immunology | AuthorChoice
    Pharmacological Inhibition of β3 Integrin Reduces the Inflammatory Toxicities Caused by Oncolytic Adenovirus without Compromising Anticancer Activity
    Ashley Browne, Laura A. Tookman, Carin K. Ingemarsdotter, Russell D. Bouwman, Katrina Pirlo, Yaohe Wang, Iain A. McNeish and Michelle Lockley
    Cancer Res July 15 2015 75 (14) 2811-2821; DOI:10.1158/0008-5472.CAN-14-3761

    This work describes a novel and clinically feasible strategy to facilitate the safe delivery of systemic viral anticancer therapies by using clinically available β3 integrin inhibitors to control the problematic inflammatory side effects induced by these effective anticancer agents.

  • Microenvironment and Immunology
    Definition of Prostaglandin E2–EP2 Signals in the Colon Tumor Microenvironment That Amplify Inflammation and Tumor Growth
    Xiaojun Ma, Tomohiro Aoki, Tatsuaki Tsuruyama and Shuh Narumiya
    Cancer Res July 15 2015 75 (14) 2822-2832; DOI:10.1158/0008-5472.CAN-15-0125

    These findings show how prostaglandin signaling in neutrophils and cancer-associated fibroblasts in the colorectal tumor microenvironment shape its inflammatory character, providing a mechanistic rationale to use EP2 antagonists as an alternative to aspirin for chemoprevention.

Molecular and Cellular Pathobiology

Prevention and Epidemiology

  • Prevention and Epidemiology
    Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer
    Alina Lemnrau, Mark N. Brook, Olivia Fletcher, Penny Coulson, Katarzyna Tomczyk, Michael Jones, Alan Ashworth, Anthony Swerdlow, Nick Orr and Montserrat Garcia-Closas
    Cancer Res July 15 2015 75 (14) 2844-2850; DOI:10.1158/0008-5472.CAN-14-1692

    The use of mtDNA copy number measured in blood samples prior to diagnosis is associated with elevated risk of developing breast cancer.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Enhanced MET Translation and Signaling Sustains K-Ras–Driven Proliferation under Anchorage-Independent Growth Conditions
    Saori Fujita-Sato, Jacqueline Galeas, Morgan Truitt, Cameron Pitt, Anatoly Urisman, Sourav Bandyopadhyay, Davide Ruggero and Frank McCormick
    Cancer Res July 15 2015 75 (14) 2851-2862; DOI:10.1158/0008-5472.CAN-14-1623

    These results suggest that to drive malignant cell growth K-Ras requires the activity of the Met receptor kinase, a therapeutic target already being explored in the clinic, with implications in addressing the long-standing challenge of how to attack K-Ras–driven human tumors.

  • Therapeutics, Targets, and Chemical Biology
    Vacuolar-ATPase Inhibition Blocks Iron Metabolism to Mediate Therapeutic Effects in Breast Cancer
    Lina S. Schneider, Karin von Schwarzenberg, Thorsten Lehr, Melanie Ulrich, Rebekka Kubisch-Dohmen, Johanna Liebl, Dirk Trauner, Dirk Menche and Angelika M. Vollmar
    Cancer Res July 15 2015 75 (14) 2863-2874; DOI:10.1158/0008-5472.CAN-14-2097

    Inhibition of a vacuolar ATPase that functions as an ion pump in maintaining cellular pathophysiology in cancer appears to selectively disturb iron metabolic pathways, thereby blocking tumor growth.

  • Therapeutics, Targets, and Chemical Biology
    An In Vivo Method to Identify microRNA Targets Not Predicted by Computation Algorithms: p21 Targeting by miR-92a in Cancer
    Xiaoping Su, Huaming Wang, Wei Ge, Mingjin Yang, Jin Hou, Taoyong Chen, Nan Li and Xuetao Cao
    Cancer Res July 15 2015 75 (14) 2875-2885; DOI:10.1158/0008-5472.CAN-14-2218

    This study describes a new method for in vivo miRNA precipitation (miRIP), which can identify target-specific miRNAs for an mRNA not otherwise identified by current in silico methods.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Secalonic Acid-D Represses HIF1α/VEGF-Mediated Angiogenesis by Regulating the Akt/mTOR/p70S6K Signaling Cascade
    Santosh Kumar Guru, Anup Singh Pathania, Suresh Kumar, Deshidi Ramesh, Manjeet Kumar, Satiander Rana, Ajay Kumar, Fayaz Malik, P.R. Sharma, B.K. Chandan, Sundeep Jaglan, J.P. Sharma, Bhahwal Ali Shah, Sheikh Abdullah Tasduq, Surrinder K. Lattoo, Abdul Faruk, A.K. Saxena, R.A. Vishwakarma and Shashi Bhushan
    Cancer Res July 15 2015 75 (14) 2886-2896; DOI:10.1158/0008-5472.CAN-14-2312

    These findings offer a preclinical validation of the antiangiogenic uses for a novel mycotoxin in the generalized treatment of solid tumors.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine
    Michelle L. Stewart, Pablo Tamayo, Andrew J. Wilson, Stephanie Wang, Yun Min Chang, Jong W. Kim, Dineo Khabele, Alykhan F. Shamji and Stuart L. Schreiber
    Cancer Res July 15 2015 75 (14) 2897-2906; DOI:10.1158/0008-5472.CAN-14-2860

    These findings define a mechanistic basis and a biomarker to predict the sensitivity of ovarian cancer cells to a cytotoxic DNA methyltransferase inhibitor, with potentially generalizable applications.

  • Therapeutics, Targets, and Chemical Biology
    Targeting Pancreatic Cancer Metastasis by Inhibition of Vav1, a Driver of Tumor Cell Invasion
    Gina L. Razidlo, Christopher Magnine, Arthur C. Sletten, Rachel M. Hurley, Luciana L. Almada, Martin E. Fernandez-Zapico, Baoan Ji and Mark A. McNiven
    Cancer Res July 15 2015 75 (14) 2907-2915; DOI:10.1158/0008-5472.CAN-14-3103

    These findings offer a preclinical rationale for repositioning the well-established drug azathioprine to inhibit metastasis of deadly pancreatic cancers.

  • Therapeutics, Targets, and Chemical Biology
    Evidence Suggesting That Discontinuous Dosing of ALK Kinase Inhibitors May Prolong Control of ALK+ Tumors
    Amit Dipak Amin, Soumya S. Rajan, Winnie S. Liang, Praechompoo Pongtornpipat, Matthew J. Groysman, Edgar O. Tapia, Tara L. Peters, Lori Cuyugan, Jonathan Adkins, Lisa M. Rimsza, Yves A. Lussier, Soham D. Puvvada and Jonathan H. Schatz
    Cancer Res July 15 2015 75 (14) 2916-2927; DOI:10.1158/0008-5472.CAN-14-3437

    This important study shows how kinase upregulation in cancer cells can foster resistance to a kinase inhibitory drug, but that this upregulation also sensitizes cells to kinase-mediated toxicities that can be exploited by altering the drug dosing schedule, as a strategy to defeat the drug resistance.

  • Therapeutics, Targets, and Chemical Biology
    Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti–PD-L1 Antibodies
    Sandra Heskamp, Willemijn Hobo, Janneke D.M. Molkenboer-Kuenen, Daniel Olive, Wim J.G. Oyen, Harry Dolstra and Otto C. Boerman
    Cancer Res July 15 2015 75 (14) 2928-2936; DOI:10.1158/0008-5472.CAN-14-3477

    PD-L1 expression in tumors is important for PD-1/PD-L1–based therapeutics and can be monitored noninvasively using SPECT/CT imaging, which may more readily enable patient selection for trials of this type of antibody-based immune checkpoint therapy.

Tumor and Stem Cell Biology

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Cancer Research: 75 (14)
July 2015
Volume 75, Issue 14

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