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Table of Contents

Breaking Advances

Reviews

Perspective

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    Oncogenic RAS Regulates Long Noncoding RNA Orilnc1 in Human Cancer
    Dongmei Zhang, Gao Zhang, Xiaowen Hu, Lawrence Wu, Yi Feng, Sidan He, Youyou Zhang, Zhongyi Hu, Lu Yang, Tian Tian, Weiting Xu, Zhi Wei, Yiling Lu, Keith T. Flaherty, Xiaomin Zhong, Gordon B. Mills, Phyllis A. Gimotty, Xiaowei Xu, Meenhard Herlyn and Lin Zhang
    Cancer Res July 15 2017 77 (14) 3745-3757; DOI:10.1158/0008-5472.CAN-16-1768

    RAS-responding effector genes that control cell-cycle transit rely upon coordinate upregulation of a long non-coding RNA, implicating it as a possible therapeutic target in RAS-driven cancers.

  • Molecular and Cellular Pathobiology
    ETV1-Positive Cells Give Rise to BRAFV600E-Mutant Gastrointestinal Stromal Tumors
    Leili Ran, Devan Murphy, Jessica Sher, Zhen Cao, Shangqian Wang, Edward Walczak, Youxin Guan, Yuanyuan Xie, Shipra Shukla, Yu Zhan, Cristina R. Antonescu, Yu Chen and Ping Chi
    Cancer Res July 15 2017 77 (14) 3758-3765; DOI:10.1158/0008-5472.CAN-16-3510

    This study offers a useful in vivo model of human sporadic forms of BRAF-mutant GIST to help unravel its pathogenesis and therapeutic response to novel experimental agents.

Tumor and Stem Cell Biology

  • Tumor and Stem Cell Biology
    ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas
    Katie B. Grausam, Samuel D.R. Dooyema, Laure Bihannic, Hasitha Premathilake, A. Sorana Morrissy, Antoine Forget, Amanda M. Schaefer, Justin H. Gundelach, Slobodan Macura, Diane M. Maher, Xin Wang, Alex H. Heglin, Xijin Ge, Erliang Zeng, Stephanie Puget, Indra Chandrasekar, Kameswaran Surendran, Richard J. Bram, Ulrich Schüller, Michael D. Talyor, Olivier Ayrault and Haotian Zhao
    Cancer Res July 15 2017 77 (14) 3766-3777; DOI:10.1158/0008-5472.CAN-16-1836

    These findings illuminate a metastasis pathway in the common pediatric brain tumor medulloblastoma, which offers possible theranostic opportunities.

  • Tumor and Stem Cell Biology
    An miRNA Expression Signature for the Human Colonic Stem Cell Niche Distinguishes Malignant from Normal Epithelia
    Vignesh Viswanathan, Shirish Damle, Tao Zhang, Lynn Opdenaker, Shirin Modarai, Monica Accerbi, Skye Schmidt, Pamela Green, Deni Galileo, Juan Palazzo, Jeremy Fields, Sepehr Haghighat, Isidore Rigoutsos, Greg Gonye and Bruce M. Boman
    Cancer Res July 15 2017 77 (14) 3778-3790; DOI:10.1158/0008-5472.CAN-16-2388

    By defining miRNAs that sustain stem cells in the crypts of normal colon tissue, this study illuminates a pivotal mechanism through which cancer stem-like cells may be created to seed colorectal cancers.

  • Tumor and Stem Cell Biology
    Akt Signaling Is Sustained by a CD44 Splice Isoform–Mediated Positive Feedback Loop
    Sali Liu and Chonghui Cheng
    Cancer Res July 15 2017 77 (14) 3791-3801; DOI:10.1158/0008-5472.CAN-16-2545

    This important paper describes the discovery of a positive feedback mechanism that sustains PI3K/Akt signaling in tumor cells that lack PI3K/Akt mutations, illuminating the nearly universal role this pathway has in tumor cell survival.

  • Tumor and Stem Cell Biology | AuthorChoice
    NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor Suppressor PML in Breast Cancer
    Hanan S. Elsarraj, Kelli E. Valdez, Yan Hong, Sandra L. Grimm, Lawrence R. Ricci, Fang Fan, Ossama Tawfik, Lisa May, Therese Cusick, Marc Inciardi, Mark Redick, Jason Gatewood, Onalisa Winblad, Susan Hilsenbeck, Dean P. Edwards, Christy R. Hagan, Andrew K. Godwin, Carol Fabian and Fariba Behbod
    Cancer Res July 15 2017 77 (14) 3802-3813; DOI:10.1158/0008-5472.CAN-16-2794

    These findings challenge the notion of the detrimental role of estrogen plus progesterone in breast cancer, revealing a signaling cascade that upregulates the tumor suppressor protein PML in response to both hormones.

  • Tumor and Stem Cell Biology
    A Systematic Analysis of Oncogenic Gene Fusions in Primary Colon Cancer
    Wigard P. Kloosterman, Robert R.J. Coebergh van den Braak, Mark Pieterse, Markus J. van Roosmalen, Anieta M. Sieuwerts, Christina Stangl, Ronne Brunekreef, Zarina S. Lalmahomed, Salo Ooft, Anne van Galen, Marcel Smid, Armel Lefebvre, Fried Zwartkruis, John W.M. Martens, John A. Foekens, Katharina Biermann, Marco J. Koudijs, Jan N.M. Ijzermans and Emile E. Voest
    Cancer Res July 15 2017 77 (14) 3814-3822; DOI:10.1158/0008-5472.CAN-16-3563

    This deep sequencing study of stage I-III colon cancer specimens identifies novel oncogenic gene fusions in colorectal cancer that may drive malignant progression and offer new targets for personalized therapy.

  • Tumor and Stem Cell Biology
    Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells
    Kyle P. Feeley, Clare M. Adams, Ramkrishna Mitra and Christine M. Eischen
    Cancer Res July 15 2017 77 (14) 3823-3833; DOI:10.1158/0008-5472.CAN-17-0809

    By refuting the prevailing view that cells lacking Mdm2 can survive if p53 is also absent, this important study provides a therapeutic rationale for targeting Mdm2 to eliminate p53-null lymphomas and sarcomas.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology
    Therapeutic Rationale to Target Highly Expressed CDK7 Conferring Poor Outcomes in Triple-Negative Breast Cancer
    Bo Li, Triona Ni Chonghaile, Yue Fan, Stephen F. Madden, Rut Klinger, Aisling E. O'Connor, Louise Walsh, Gillian O'Hurley, Girish Mallya Udupi, Jesuchristopher Joseph, Finbarr Tarrant, Emer Conroy, Alexander Gaber, Suet-Feung Chin, Helen A. Bardwell, Elena Provenzano, John Crown, Thierry Dubois, Sabine Linn, Karin Jirstrom, Carlos Caldas, Darran P. O'Connor and William M. Gallagher
    Cancer Res July 15 2017 77 (14) 3834-3845; DOI:10.1158/0008-5472.CAN-16-2546

    This potentially seminal study offers preclinical proof of concept for combining CDK7 and BCL-2/BCL-XL inhibitors as a mechanism-based therapeutic strategy to improve the management of aggressive triple-negative breast cancers, which still lack effective biomarkers and precision treatment approaches.

  • Therapeutics, Targets, and Chemical Biology
    Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression
    Lucia Casadei, Federica Calore, Chad J. Creighton, Michele Guescini, Kara Batte, O. Hans Iwenofu, Abeba Zewdu, Danielle A. Braggio, Kate Lynn Bill, Paolo Fadda, Francesca Lovat, Gonzalo Lopez, Pierluigi Gasparini, James L. Chen, Raleigh D. Kladney, Gustavo Leone, Dina Lev, Carlo M. Croce and Raphael E. Pollock
    Cancer Res July 15 2017 77 (14) 3846-3856; DOI:10.1158/0008-5472.CAN-16-2984

    Two extracellular vesicle-derived microRNAs are found to drive liposarcoma progression by stimulating the secretion of proinflammatory IL6 from tumor-associated macrophages, offering new theranostic opportunities in this cancer setting.

  • Therapeutics, Targets, and Chemical Biology
    Nicotinic Acid Phosphoribosyltransferase Regulates Cancer Cell Metabolism, Susceptibility to NAMPT Inhibitors, and DNA Repair
    Francesco Piacente, Irene Caffa, Silvia Ravera, Giovanna Sociali, Mario Passalacqua, Valerio G. Vellone, Pamela Becherini, Daniele Reverberi, Fiammetta Monacelli, Alberto Ballestrero, Patrizio Odetti, Antonia Cagnetta, Michele Cea, Aimable Nahimana, Michel Duchosal, Santina Bruzzone and Alessio Nencioni
    Cancer Res July 15 2017 77 (14) 3857-3869; DOI:10.1158/0008-5472.CAN-16-3079

    Targeting a second enzyme involved in NAD+ biosynthesis overcomes the resistance to NAMPT inhibitors observed in clinical trials, offering a path toward new therapies.

  • Therapeutics, Targets, and Chemical Biology
    CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib
    Triparna Sen, Pan Tong, C. Allison Stewart, Sandra Cristea, Aly Valliani, David S. Shames, Abena B. Redwood, You Hong Fan, Lerong Li, Bonnie S. Glisson, John D. Minna, Julien Sage, Don L. Gibbons, Helen Piwnica-Worms, John V. Heymach, Jing Wang and Lauren Averett Byers
    Cancer Res July 15 2017 77 (14) 3870-3884; DOI:10.1158/0008-5472.CAN-16-3409

    These findings demonstrate potent antitumor activity of targeting CHK1 in chemosensitive and chemoresistant models of small cell lung cancer, especially those with MYC amplification or overexpression.

  • Therapeutics, Targets, and Chemical Biology
    Venetoclax Synergizes with Radiotherapy for Treatment of B-cell Lymphomas
    Shyril O'Steen, Damian J. Green, Ajay K. Gopal, Johnnie J. Orozco, Aimee L. Kenoyer, Yukang Lin, D. Scott Wilbur, Donald K. Hamlin, Darrell R. Fisher, Mark D. Hylarides, Theodore A. Gooley, Amelia Waltman, Brian G. Till and Oliver W. Press
    Cancer Res July 15 2017 77 (14) 3885-3893; DOI:10.1158/0008-5472.CAN-17-0082

    Combining the BCL-2 inhibitor venetoclax with radioimmunotherapy yields a synergistic therapeutic response in preclinical models of three lymphoma subtypes, with optimal dosing curing all mice with no detectable toxicity.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination
    Hong Jiang, Yisel Rivera-Molina, Candelaria Gomez-Manzano, Karen Clise-Dwyer, Laura Bover, Luis M. Vence, Ying Yuan, Frederick F. Lang, Carlo Toniatti, Mohammad B. Hossain and Juan Fueyo
    Cancer Res July 15 2017 77 (14) 3894-3907; DOI:10.1158/0008-5472.CAN-17-0468

    Combining an oncolytic virus with an immune checkpoint drug creates an in situ autologous vaccine effect, establishing a tumor-specific treatment that is both efficacious and durable.

Integrated Systems and Technologies

  • Integrated Systems and Technologies | AuthorChoice
    Pharmacokinetics and Drug Interactions Determine Optimum Combination Strategies in Computational Models of Cancer Evolution
    Shaon Chakrabarti and Franziska Michor
    Cancer Res July 15 2017 77 (14) 3908-3921; DOI:10.1158/0008-5472.CAN-16-2871

    In seeking to improve responses to combination therapy, a model that incorporates parameters for cancer evolution suggests variations in dosing regimens that can safely increase therapeutic efficacy, with immediate clinical implications.

  • Integrated Systems and Technologies | AuthorChoice
    Somatic Mutations Drive Distinct Imaging Phenotypes in Lung Cancer
    Emmanuel Rios Velazquez, Chintan Parmar, Ying Liu, Thibaud P. Coroller, Gisele Cruz, Olya Stringfield, Zhaoxiang Ye, Mike Makrigiorgos, Fiona Fennessy, Raymond H. Mak, Robert Gillies, John Quackenbush and Hugo J.W.L. Aerts
    Cancer Res July 15 2017 77 (14) 3922-3930; DOI:10.1158/0008-5472.CAN-17-0122

    The findings of this important study add to the understanding of the biological basis for tumor phenotypes, which can be quantified by medical imaging.

  • Integrated Systems and Technologies
    Noninvasive Interrogation of DLL3 Expression in Metastatic Small Cell Lung Cancer
    Sai Kiran Sharma, Jacob Pourat, Dalya Abdel-Atti, Sean D. Carlin, Alessandra Piersigilli, Alexander J. Bankovich, Eric E. Gardner, Omar Hamdy, Kumiko Isse, Sheila Bheddah, Joseph Sandoval, Kristen M. Cunanan, Eric B. Johansen, Viola Allaj, Vikram Sisodiya, David Liu, Brian M. Zeglis, Charles M. Rudin, Scott J. Dylla, John T. Poirier and Jason S. Lewis
    Cancer Res July 15 2017 77 (14) 3931-3941; DOI:10.1158/0008-5472.CAN-17-0299

    A companion diagnostic PET imaging agent can enable clinicians to rapidly identify small cell lung cancer patients most likely to benefit from treatment with a Notch ligand-targeting therapy, despite low levels of ligand expression on the surface of the cancer cells.

  • Integrated Systems and Technologies
    Highly Accurate Detection of Cancer In Situ with Intraoperative, Label-Free, Multimodal Optical Spectroscopy
    Michael Jermyn, Jeanne Mercier, Kelly Aubertin, Joannie Desroches, Kirk Urmey, Jason Karamchandiani, Eric Marple, Marie-Christine Guiot, Frederic Leblond and Kevin Petrecca
    Cancer Res July 15 2017 77 (14) 3942-3950; DOI:10.1158/0008-5472.CAN-17-0668

    These findings present the design, development, and clinical testing of a cancer detection system of nearly perfect accuracy that can improve surgical resections while in the operating room.

Prevention and Epidemiology

  • Prevention and Epidemiology
    Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium
    Jennifer Ose, Elizabeth M. Poole, Helena Schock, Matti Lehtinen, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Kala Visvanathan, Kathy Helzlsouer, Julie E. Buring, I-Min Lee, Anne Tjønneland, Laure Dossus, Antonia Trichopoulou, Giovanna Masala, N. Charlotte Onland-Moret, Elisabete Weiderpass, Eric J. Duell, Annika Idahl, Ruth C. Travis, Sabina Rinaldi, Melissa A. Merritt, Britton Trabert, Nicolas Wentzensen, Shelley S. Tworoger, Rudolf Kaaks and Renée T. Fortner
    Cancer Res July 15 2017 77 (14) 3951-3960; DOI:10.1158/0008-5472.CAN-16-3322

    These findings show significant differences in the associations between circulating androgen concentrations and invasive ovarian cancer risk by subtype, underscoring the importance of examining etiologic differences by subtype.

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