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Table of Contents

Breaking Advances

Reviews

Meeting Report

Integrated Systems and Technologies

Microenvironment and Immunology

  • Microenvironment and Immunology
    Lysyl Oxidase Is a Strong Determinant of Tumor Cell Colonization in Bone
    Caroline Reynaud, Laura Ferreras, Paola Di Mauro, Casina Kan, Martine Croset, Edith Bonnelye, Floriane Pez, Clémence Thomas, Géraldine Aimond, Antoine E. Karnoub, Marie Brevet and Philippe Clézardin
    Cancer Res January 15 2017 77 (2) 268-278; DOI:10.1158/0008-5472.CAN-15-2621

    These findings reveal a targetable mechanism that could be exploited to block metastasis of colorectal cancer to bone, an essentially untreatable form of the disease.

  • Microenvironment and Immunology
    Macrophage-Secreted TNFα and TGFβ1 Influence Migration Speed and Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways
    Ran Li, Jess D. Hebert, Tara A. Lee, Hao Xing, Alexandra Boussommier-Calleja, Richard O. Hynes, Douglas A. Lauffenburger and Roger D. Kamm
    Cancer Res January 15 2017 77 (2) 279-290; DOI:10.1158/0008-5472.CAN-16-0442

    These findings identify independent cooperating pathways through which macrophages control the speed and persistence of cancer cell migration in 3D tissue microenvironments.

  • Microenvironment and Immunology
    Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells
    Ibrahim M. Sektioglu, Rafael Carretero, Nadja Bulbuc, Tobias Bald, Thomas Tüting, Alexander Y. Rudensky and Günter J. Hämmerling
    Cancer Res January 15 2017 77 (2) 291-302; DOI:10.1158/0008-5472.CAN-16-0993

    These findings elucidate a novel contribution of basophils to tumor rejection that can be exploited to enhance the efficacy of cancer immunotherapy.

  • Microenvironment and Immunology | AuthorChoice
    MIF-Induced Stromal PKCβ/IL8 Is Essential in Human Acute Myeloid Leukemia
    Amina M. Abdul-Aziz, Manar S. Shafat, Tarang K. Mehta, Federica Di Palma, Matthew J. Lawes, Stuart A. Rushworth and Kristian M. Bowles
    Cancer Res January 15 2017 77 (2) 303-311; DOI:10.1158/0008-5472.CAN-16-1095

    In identifying the bidirectional MIF/IL8 survival mechanism between AML cells and bone marrow-derived mesenchymal stromal cells, this study provides a rationale to therapeutically target this protumoral feedback loop.

  • Microenvironment and Immunology
    PolyI:C and CpG Synergize with Anti-ErbB2 mAb for Treatment of Breast Tumors Resistant to Immune Checkpoint Inhibitors
    Roxanne Charlebois, Bertrand Allard, David Allard, Laurence Buisseret, Martin Turcotte, Sandra Pommey, Pavel Chrobak and John Stagg
    Cancer Res January 15 2017 77 (2) 312-319; DOI:10.1158/0008-5472.CAN-16-1873

    Immune stimulating polyI:C and CpG oligodeoxynucleotides that have been used safely in clinical trials are found to powerfully enhance the therapeutic efficacy of HER2 monoclonal antibody drugs.

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    IKBKE Is Required during KRAS-Induced Pancreatic Tumorigenesis
    Mihir Rajurkar, Kyvan Dang, Maite G. Fernandez-Barrena, Xiangfan Liu, Martin E. Fernandez-Zapico, Brian C. Lewis and Junhao Mao
    Cancer Res January 15 2017 77 (2) 320-329; DOI:10.1158/0008-5472.CAN-15-1684

    These findings offer preclinical proof of concept for combined inhibition of two key growth and survival signaling pathways as a therapeutic strategy to kill pancreatic cancer cells.

  • Molecular and Cellular Pathobiology | AuthorChoice
    KLF6 Suppresses Metastasis of Clear Cell Renal Cell Carcinoma via Transcriptional Repression of E2F1
    Yu Gao, Hongzhao Li, Xin Ma, Yang Fan, Dong Ni, Yu Zhang, Qingbo Huang, Kan Liu, Xintao Li, Lei Wang, Liangyou Gu, Yuanxin Yao, Qing Ai, Qingshan Du, Erlin Song and Xu Zhang
    Cancer Res January 15 2017 77 (2) 330-342; DOI:10.1158/0008-5472.CAN-16-0348

    A key mediator of metastasis in clear cell renal cell carcinoma acts via a noval regulatory axis, suggesting a general strategy to improve management of this disease.

  • Molecular and Cellular Pathobiology
    Molecular Chaperone HSP90 Is Necessary to Prevent Cellular Senescence via Lysosomal Degradation of p14ARF
    Su Yeon Han, Aram Ko, Haruhisa Kitano, Chel Hun Choi, Min-Sik Lee, Jinho Seo, Junya Fukuoka, Soo-Youl Kim, Stephen M. Hewitt, Joon-Yong Chung and Jaewhan Song
    Cancer Res January 15 2017 77 (2) 343-354; DOI:10.1158/0008-5472.CAN-16-0613

    In elucidating how the tumor suppressor p14ARF is degraded, this study has implications for prognosis and treatment or p14ARF-expressing lung cancers.

  • Molecular and Cellular Pathobiology
    Vitamin D3 Prevents Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing Receptor Upregulation
    Sophie Bernichtein, Natascha Pigat, Nicolas Barry Delongchamps, Florence Boutillon, Virginie Verkarre, Philippe Camparo, Edouard Reyes-Gomez, Arnaud Méjean, Stéphane M. Oudard, Eve M. Lepicard, Mélanie Viltard, Jean-Claude Souberbielle, Gérard Friedlander, Thierry Capiod and Vincent Goffin
    Cancer Res January 15 2017 77 (2) 355-365; DOI:10.1158/0008-5472.CAN-16-0687

    Opposing effects of calcium and vitamin D in prostate cancer progression provide a paradigm to evaluate calcium intake and to consider vitamin D supplementation in patients on active surveillance for low-risk prostate cancer.

  • Molecular and Cellular Pathobiology | AuthorChoice
    ZIC5 Drives Melanoma Aggressiveness by PDGFD-Mediated Activation of FAK and STAT3
    Reiko Satow, Tomomi Nakamura, Chiaki Kato, Miku Endo, Mana Tamura, Ryosuke Batori, Shiori Tomura, Yumi Murayama and Kiyoko Fukami
    Cancer Res January 15 2017 77 (2) 366-377; DOI:10.1158/0008-5472.CAN-16-0991

    An siRNA-based screen of neural crest cells from which melanocytes are derived identifies candidate targets to attack melanoma and to overcome drug resistance in this disease.

  • Molecular and Cellular Pathobiology
    Androgen-Dependent Repression of ERRγ Reprograms Metabolism in Prostate Cancer
    Étienne Audet-Walsh, Tracey Yee, Shawn McGuirk, Mathieu Vernier, Carlo Ouellet, Julie St-Pierre and Vincent Giguère
    Cancer Res January 15 2017 77 (2) 378-389; DOI:10.1158/0008-5472.CAN-16-1204

    Metabolic insights into how the androgen receptor affects the estrogen-related receptor ERRg in prostate cancer suggests new routes for its therapeutic management.

  • Molecular and Cellular Pathobiology
    Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia
    Ling-Wen Ding, Qiao-Yang Sun, Kar-Tong Tan, Wenwen Chien, Anand Mayakonda Thippeswamy, Allen Eng Juh Yeoh, Norihiko Kawamata, Yasunobu Nagata, Jin-Fen Xiao, Xin-Yi Loh, De-Chen Lin, Manoj Garg, Yan-Yi Jiang, Liang Xu, Su-Lin Lim, Li-Zhen Liu, Vikas Madan, Masashi Sanada, Lucia Torres Fernández, Hema Preethi, Michael Lill, Hagop M. Kantarjian, Steven M. Kornblau, Satoru Miyano, Der-Cherng Liang, Seishi Ogawa, Lee-Yung Shih, Henry Yang and H. Phillip Koeffler
    Cancer Res January 15 2017 77 (2) 390-400; DOI:10.1158/0008-5472.CAN-16-1303

    By providing a detailed mutational portrait of pediatric acute lymphocytic leukemias, this study suggests how to target drug-resistant tumors and develop less toxic targeted therapies.

  • Molecular and Cellular Pathobiology
    Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase
    Zijie Feng, Lei Wang, Yanmei Sun, Zongzhe Jiang, John Domsic, Chiying An, Bowen Xing, Jingjing Tian, Xiuheng Liu, David C. Metz, Xiaolu Yang, Ronen Marmorstein, Xiaosong Ma and Xianxin Hua
    Cancer Res January 15 2017 77 (2) 401-411; DOI:10.1158/0008-5472.CAN-16-1567

    This study suggesting new insights into tumor suppressor interplay in epigenetic regulation of neuroendocrine tumors may impact decisions about their therapy.

  • Molecular and Cellular Pathobiology | AuthorChoice
    Polycomb-Mediated Disruption of an Androgen Receptor Feedback Loop Drives Castration-Resistant Prostate Cancer
    Ka-wing Fong, Jonathan C. Zhao, Jung Kim, Shangze Li, Yeqing A. Yang, Bing Song, Laure Rittie, Ming Hu, Ximing Yang, Bernard Perbal and Jindan Yu
    Cancer Res January 15 2017 77 (2) 412-422; DOI:10.1158/0008-5472.CAN-16-1949

    These provocative results identify an intracellular function of a matricellular protein in directing cytosolic regulation of androgen receptor signaling and prostate cancer progression.

  • Molecular and Cellular Pathobiology
    Integrative Comparison of mRNA Expression Patterns in Breast Cancers from Caucasian and Asian Americans with Implications for Precision Medicine
    Yanxia Shi, Albert Steppi, Ye Cao, Jianan Wang, Max M. He, Liren Li and Jinfeng Zhang
    Cancer Res January 15 2017 77 (2) 423-433; DOI:10.1158/0008-5472.CAN-16-1959

    Genetic associations identified in this study may enable a more focused study of genotypic differences that can explain the disparity in BRCA incidence and mortality rates between Asian and Caucasian patient populations in the U.S.

  • Molecular and Cellular Pathobiology
    Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton
    Karineh Kazazian, Christopher Go, Hannah Wu, Olga Brashavitskaya, Roland Xu, James W. Dennis, Anne-Claude Gingras and Carol J. Swallow
    Cancer Res January 15 2017 77 (2) 434-447; DOI:10.1158/0008-5472.CAN-16-2060

    These findings reveal a novel role for Plk4 in promoting cancer invasion and metastasis through regulation of Arp2/3-mediated actin cytoskeletal rearrangement, thus validating Plk4 as a viable therapeutic target in cancer treatment.

  • Molecular and Cellular Pathobiology
    Chemopreventive Effects of ROS Targeting in a Murine Model of BRCA1-Deficient Breast Cancer
    Mo Li, Qian Chen and Xiaochun Yu
    Cancer Res January 15 2017 77 (2) 448-458; DOI:10.1158/0008-5472.CAN-16-2350

    This potentially seminal study suggests an answer to the long-standing question of why germline BRCA1 mutations cause tissue-specific tumors, with immediate implications for evaluating suitable antioxidant modalities as a strategy to mitigate the risks of familial breast cancer increased by BRCA1 mutation.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Quantification of Pathway Cross-talk Reveals Novel Synergistic Drug Combinations for Breast Cancer
    Samira Jaeger, Ana Igea, Rodrigo Arroyo, Victor Alcalde, Begoña Canovas, Modesto Orozco, Angel R. Nebreda and Patrick Aloy
    Cancer Res January 15 2017 77 (2) 459-469; DOI:10.1158/0008-5472.CAN-16-0097

    This study uses a computational approach to discover synergistic combinations between targeted drugs to treat breast cancer, with the capability of providing broadspectrum utility across several cancer types.

  • Therapeutics, Targets, and Chemical Biology
    Transcriptional Selectivity of Epigenetic Therapy in Cancer
    Takahiro Sato, Matteo Cesaroni, Woonbok Chung, Shoghag Panjarian, Anthony Tran, Jozef Madzo, Yasuyuki Okamoto, Hanghang Zhang, Xiaowei Chen, Jaroslav Jelinek and Jean-Pierre J. Issa
    Cancer Res January 15 2017 77 (2) 470-481; DOI:10.1158/0008-5472.CAN-16-0834

    In providing a comprehensive analysis of the specificity of epigenetic therapy in cancer, this study shows how combined targeting of DNA and histone methylation may offer an improved efficacy of this type of therapy for cancer treatment.

  • Therapeutics, Targets, and Chemical Biology
    EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance
    Xiaohu Zheng, Xiaolei Fan, Binqing Fu, Meijuan Zheng, Aimei Zhang, Kai Zhong, Jialai Yan, Rui Sun, Zhigang Tian and Haiming Wei
    Cancer Res January 15 2017 77 (2) 482-493; DOI:10.1158/0008-5472.CAN-16-0842

    This study shows how yet another cancer celltargeting strategy actually mediates its efficacy by modulating the immune system, a growing theme in targeted drug development.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Aurora A and NF-κB Survival Pathway Drive Chemoresistance in Acute Myeloid Leukemia via the TRAF-Interacting Protein TIFA
    Tong-You Wade Wei, Pei-Yu Wu, Ting-Jung Wu, Hsin-An Hou, Wen-Chien Chou, Chieh-Lin Jerry Teng, Chih-Ru Lin, Jo-Mei Maureen Chen, Ting-Yang Lin, Hsiang-Chun Su, Chia-Chi Flora Huang, Chang-Tze Ricky Yu, Shih-Lan Hsu, Hwei-Fang Tien and Ming-Daw Tsai
    Cancer Res January 15 2017 77 (2) 494-508; DOI:10.1158/0008-5472.CAN-16-1004

    These findings show how a survival signaling pathway mediated by a key mitotic regulator can be targeted to enhance the chemosensitivity of deadly leukemias.

  • Therapeutics, Targets, and Chemical Biology | AuthorChoice
    Genomic Profiling of a Large Set of Diverse Pediatric Cancers Identifies Known and Novel Mutations across Tumor Spectra
    Juliann Chmielecki, Mark Bailey, Jie He, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M. Frampton, James X. Sun, Samantha Morley, Daniel Spritz, Siraj Ali, Laurie Gay, Rachel L. Erlich, Jeffrey S. Ross, Joana Buxhaku, Hilary Davies, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A. Miller, Philip J. Stephens, Katherine A. Janeway, John M. Maris, Soheil Meshinchi, Trevor J. Pugh, Jack F. Shern and Doron Lipson
    Cancer Res January 15 2017 77 (2) 509-519; DOI:10.1158/0008-5472.CAN-16-1106

    Analysis of an aggregate genomic dataset for pediatric tumors may illuminate novel therapeutic targets, validate oncogenic mechanisms, guide treatment decisions, and design appropriate clinical trials for children with cancer.

  • Therapeutics, Targets, and Chemical Biology
    Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment
    Yang Liu, Srilakshmi Pandeswara, Vinh Dao, Álvaro Padrón, Justin M. Drerup, Shunhua Lao, Aijie Liu, Vincent Hurez and Tyler J. Curiel
    Cancer Res January 15 2017 77 (2) 520-531; DOI:10.1158/0008-5472.CAN-16-1140

    These findings show how novel low-dose administration of mTOR inhibitors can effectively cooperate with, rather than antagonize immunotherapy, resuscitating interest in mTOR-targeting therapies, which have otherwise been mainly disappointing in clinical trials.

  • Therapeutics, Targets, and Chemical Biology
    Circadian Clock Gene Bmal1 Inhibits Tumorigenesis and Increases Paclitaxel Sensitivity in Tongue Squamous Cell Carcinoma
    Qingming Tang, Bo Cheng, Mengru Xie, Yatao Chen, Jiajia Zhao, Xin Zhou and Lili Chen
    Cancer Res January 15 2017 77 (2) 532-544; DOI:10.1158/0008-5472.CAN-16-1322

    By identifying a novel tumor suppressor gene that sensitizes cancer cells to paclitaxel, this study may have implications for timed chronotherapy of head and neck cancer, where this drug is used.

  • Therapeutics, Targets, and Chemical Biology
    Breast Cancer Resistance to Antiestrogens Is Enhanced by Increased ER Degradation and ERBB2 Expression
    Tomohiro Shibata, Kosuke Watari, Hiroto Izumi, Akihiko Kawahara, Satoshi Hattori, Chihiro Fukumitsu, Yuichi Murakami, Ryuji Takahashi, Uhi Toh, Ken-ichi Ito, Shigehiro Ohdo, Maki Tanaka, Masayoshi Kage, Michihiko Kuwano and Mayumi Ono
    Cancer Res January 15 2017 77 (2) 545-556; DOI:10.1158/0008-5472.CAN-16-1593

    These findings unravel a novel mechanism of resistance to antiestrogen drugs in ER+ breast cancer cells, with potential prognostic and therapeutic implications.

  • Therapeutics, Targets, and Chemical Biology
    A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents
    Antoine Azan, Peter J. Caspers, Tom C. Bakker Schut, Séverine Roy, Céline Boutros, Christine Mateus, Emilie Routier, Benjamin Besse, David Planchard, Atmane Seck, Nyam Kamsu Kom, Gorana Tomasic, Senada Koljenović, Vincent Noordhoek Hegt, Matthieu Texier, Emilie Lanoy, Alexander M.M. Eggermont, Angelo Paci, Caroline Robert, Gerwin J. Puppels and Lluis M. Mir
    Cancer Res January 15 2017 77 (2) 557-565; DOI:10.1158/0008-5472.CAN-16-1733

    This study describes a noninvasive imaging technique to rapidly assess skin toxicity caused by diverse cancer treatments, addressing a common type of side effect experienced by patients receiving cancer therapy.

  • Therapeutics, Targets, and Chemical Biology
    Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
    Vikram B. Wali, Casey G. Langdon, Matthew A. Held, James T. Platt, Gauri A. Patwardhan, Anton Safonov, Bilge Aktas, Lajos Pusztai, David F. Stern and Christos Hatzis
    Cancer Res January 15 2017 77 (2) 566-578; DOI:10.1158/0008-5472.CAN-16-1901

    Through a guided screen of FDA-approved and investigational drugs, this study suggests new treatments for aggressive triple-negative breast cancers that can be immediately translated to clinical trials.

Tumor and Stem Cell Biology

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