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Volume 16, Issue 9
1 September 2017
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    issue cover
    ABOUT THE COVER
    Irradiation therapy for head and neck cancer frequently damages normal oral tissues including the salivary glands, resulting in loss of saliva producing acinar cells and reduced saliva production. Tyrosine kinase inhibitors (TKIs) provide robust radioprotection of salivary gland function, which is associated with salivary acinar cell regeneration. The cover shows aquaporin 5 stained acinar cells in the submandibular gland of mice treated with dasastinib in conjunction with irradiation. For more details, see article by Wie and colleagues on page 1989.
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ISSN 1535-7163
EISSN 1538-8514

Highlights

Highlights of This Issue
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Small Molecule Therapeutics

Cotargeting of MEK and PDGFR/STAT3 Pathways to Treat Pancreatic Ductal Adenocarcinoma
Nisebita Sahu; Emily Chan; Felix Chu; Thinh Pham; Hartmut Koeppen; William Forrest; Mark Merchant; Jeff Settleman
View articletitled, Cotargeting of MEK and PDGFR/STAT3 Pathways to Treat Pancreatic Ductal Adenocarcinoma
Supplementary data
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Preclinical Efficacy and Molecular Mechanism of Targeting CDK7-Dependent Transcriptional Addiction in Ovarian Cancer
Zhenfeng Zhang; Huixin Peng; Xiaojie Wang; Xia Yin; Pengfei Ma; Ying Jing; Mei-Chun Cai; Jin Liu; Meiying Zhang; Shengzhe Zhang; Kaixuan Shi; Wei-Qiang Gao; Wen Di; Guanglei Zhuang
View articletitled, Preclinical Efficacy and Molecular Mechanism of Targeting CDK7-Dependent Transcriptional Addiction in Ovarian Cancer
Supplementary data
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CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest
Ashleigh M. Francis; Angela Alexander; Yanna Liu; Smruthi Vijayaraghavan; Kwang Hui Low; Dong Yang; Tuyen Bui; Neeta Somaiah; Vinod Ravi; Khandan Keyomarsi; Kelly K. Hunt
View articletitled, CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest
Supplementary data
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β-Catenin Inhibitor BC2059 Is Efficacious as Monotherapy or in Combination with Proteasome Inhibitor Bortezomib in Multiple Myeloma
Ioanna Savvidou; Tiffany Khong; Andrew Cuddihy; Catriona McLean; Stephen Horrigan; Andrew Spencer
View articletitled, β-Catenin Inhibitor BC2059 Is Efficacious as Monotherapy or in Combination with Proteasome Inhibitor Bortezomib in Multiple Myeloma
Supplementary data
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Inhibition of Hsp90 Suppresses PI3K/AKT/mTOR Signaling and Has Antitumor Activity in Burkitt Lymphoma
Lisa Giulino-Roth; Herman J. van Besien; Tanner Dalton; Jennifer E. Totonchy; Anna Rodina; Tony Taldone; Alexander Bolaender; Hediye Erdjument-Bromage; Jouliana Sadek; Amy Chadburn; Matthew J. Barth; Filemon S. Dela Cruz; Allison Rainey; Andrew L. Kung; Gabriela Chiosis; Ethel Cesarman
View articletitled, Inhibition of Hsp90 Suppresses PI3K/AKT/mTOR Signaling and Has Antitumor Activity in Burkitt Lymphoma
Supplementary data
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Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A–β-Catenin Signaling and Restricts Tumor Growth and Metastasis
Shrankhla Maheshwari; Srinivasa R. Avula; Akhilesh Singh; L. Ravithej Singh; Gopala R. Palnati; Rakesh K. Arya; Srikanth H. Cheruvu; Sudhir Shahi; Tanuj Sharma; Sanjeev Meena; Anup K. Singh; Ruchir Kant; Mohammed Riyazuddin; Himangsu K. Bora; Mohammad I. Siddiqi; Jiaur R. Gayen; Koneni V. Sashidhara; Dipak Datta
View articletitled, Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A–β-Catenin Signaling and Restricts Tumor Growth and Metastasis
Supplementary data
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Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells
Xinzhe Li; Bo Li; Zhenhong Ni; Peng Zhou; Bin Wang; Jintao He; Haojun Xiong; Fan Yang; Yaran Wu; Xilin Lyu; Yan Zhang; Yijun Zeng; Jiqin Lian; Fengtian He
View articletitled, Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells
Supplementary data
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Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells
Joshua J. Souchek; Amanda L. Davis; Tanner K. Hill; Megan B. Holmes; Bowen Qi; Pankaj K. Singh; Steven J. Kridel; Aaron M. Mohs
View articletitled, Combination Treatment with Orlistat-Containing Nanoparticles and Taxanes Is Synergistic and Enhances Microtubule Stability in Taxane-Resistant Prostate Cancer Cells
Supplementary data
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Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Pounami Samadder; Tereza Suchánková; Ondřej Hylse; Prashant Khirsariya; Fedor Nikulenkov; Stanislav Drápela; Nicol Straková; Petr Vaňhara; Kateřina Vašíčková; Hana Kolářová; Lucia Binó; Miroslava Bittová; Petra Ovesná; Peter Kollár; Radek Fedr; Milan Ešner; Josef Jaroš; Aleš Hampl; Lumír Krejčí; Kamil Paruch; Karel Souček
View articletitled, Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation
Supplementary data
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ADA-07 Suppresses Solar Ultraviolet–Induced Skin Carcinogenesis by Directly Inhibiting TOPK
Ge Gao; Tianshun Zhang; Qiushi Wang; Kanamata Reddy; Hanyong Chen; Ke Yao; Keke Wang; Eunmiri Roh; Tatyana Zykova; Weiya Ma; Joohyun Ryu; Clara Curiel-Lewandrowski; David Alberts; Sally E. Dickinson; Ann M. Bode; Ying Xing; Zigang Dong
View articletitled, ADA-07 Suppresses Solar Ultraviolet–Induced Skin Carcinogenesis by Directly Inhibiting TOPK
Supplementary data
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Large Molecule Therapeutics

Antitumor Synergism and Enhanced Survival with a Tumor Vasculature–Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide
John J. Krais; Needa Virani; Patrick H. McKernan; Quang Nguyen; Kar-Ming Fung; Vassilios I. Sikavitsas; Carla Kurkjian; Roger G. Harrison
View articletitled, Antitumor Synergism and Enhanced Survival with a Tumor Vasculature–Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide
Supplementary data
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A Potential Mechanism for ADC-Induced Neutropenia: Role of Neutrophils in Their Own Demise
Hui Zhao; Sara Gulesserian; Maria Christina Malinao; Sathish Kumar Ganesan; James Song; Mi Sook Chang; Melissa M. Williams; Zhilan Zeng; Michael Mattie; Brian A. Mendelsohn; David R. Stover; Fernando Doñate
View articletitled, A Potential Mechanism for ADC-Induced Neutropenia: Role of Neutrophils in Their Own Demise
Supplementary data
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Inhibition of Megakaryocyte Differentiation by Antibody–Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia
Hui Zhao; Sara Gulesserian; Sathish Kumar Ganesan; Jimmy Ou; Karen Morrison; Zhilan Zeng; Veronica Robles; Josh Snyder; Lisa Do; Hector Aviña; Sher Karki; David R. Stover; Fernando Doñate
View articletitled, Inhibition of Megakaryocyte Differentiation by Antibody–Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia
Supplementary data
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Author Choice
Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy
Sofia Järnum; Anna Runström; Robert Bockermann; Lena Winstedt; Max Crispin; Christian Kjellman
View articletitled, Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy
Supplementary data
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IL6 Receptor Blockade Enhances Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma
Kristen B. Long; Graham Tooker; Evan Tooker; Santiago Lombo Luque; Jae W. Lee; Xiaoqing Pan; Gregory L. Beatty
View articletitled, IL6 Receptor Blockade Enhances Chemotherapy Efficacy in Pancreatic Ductal Adenocarcinoma
Supplementary data
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A Novel Theranostic Strategy for MMP-14–Expressing Glioblastomas Impacts Survival
Suchismita Mohanty; Zixin Chen; Kai Li; Goreti Ribeiro Morais; Jessica Klockow; Ketan Yerneni; Laura Pisani; Frederick T. Chin; Siddharta Mitra; Samuel Cheshier; Edwin Chang; Sanjiv Sam Gambhir; Jianghong Rao; Paul M. Loadman; Robert A. Falconer; Heike E. Daldrup-Link
View articletitled, A Novel Theranostic Strategy for <em>MMP-14</em>–Expressing Glioblastomas Impacts Survival
Supplementary data
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Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors
Bruna F.M.M. Porchia; Ana Carolina R. Moreno; Rodrigo N. Ramos; Mariana O. Diniz; Laís Helena T.M. de Andrade; Daniela S. Rosa; José Alexandre M. Barbuto; Silvia B. Boscardin; Luís Carlos S. Ferreira
View articletitled, Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors
Supplementary data
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Cancer Biology and Signal Transduction

Inhibition of Aurora A and Aurora B Is Required for the Sensitivity of HPV-Driven Cervical Cancers to Aurora Kinase Inhibitors
David Martin; Sora Fallaha; Martina Proctor; Alexander Stevenson; Lewis Perrin; Nigel McMillan; Brian Gabrielli
View articletitled, Inhibition of Aurora A and Aurora B Is Required for the Sensitivity of HPV-Driven Cervical Cancers to Aurora Kinase Inhibitors
Supplementary data
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mTORC1 Inhibition Induces Resistance to Methotrexate and 6-Mercaptopurine in Ph+ and Ph-like B-ALL
Thanh-Trang T. Vo; J. Scott Lee; Duc Nguyen; Brandon Lui; William Pandori; Andrew Khaw; Sharmila Mallya; Mengrou Lu; Markus Müschen; Marina Konopleva; David A. Fruman
View articletitled, mTORC1 Inhibition Induces Resistance to Methotrexate and 6-Mercaptopurine in Ph<sup>+</sup> and Ph-like B-ALL
Supplementary data
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Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor
Shan Zeng; Adrian M. Seifert; Jennifer Q. Zhang; Michael J. Cavnar; Teresa S. Kim; Vinod P. Balachandran; Juan A. Santamaria-Barria; Noah A. Cohen; Michael J. Beckman; Benjamin D. Medina; Ferdinand Rossi; Megan H. Crawley; Jennifer K. Loo; Joanna H. Maltbaek; Peter Besmer; Cristina R. Antonescu; Ronald P. DeMatteo
View articletitled, Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor
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Author Choice
An In Vivo Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer
Matthew Ashenden; Antoinette van Weverwijk; Nirupa Murugaesu; Antony Fearns; James Campbell; Qiong Gao; Marjan Iravani; Clare M. Isacke
View articletitled, An <em>In Vivo</em> Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer
Supplementary data
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FBW7-Dependent Mcl-1 Degradation Mediates the Anticancer Effect of Hsp90 Inhibitors
Jingshan Tong; Shuai Tan; Zaneta Nikolovska-Coleska; Jian Yu; Fangdong Zou; Lin Zhang
View articletitled, <em>FBW7</em>-Dependent Mcl-1 Degradation Mediates the Anticancer Effect of Hsp90 Inhibitors
Supplementary data
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Tyrosine Kinase Inhibitors Protect the Salivary Gland from Radiation Damage by Inhibiting Activation of Protein Kinase C-δ
Sten M. Wie; Elizabeth Wellberg; Sana D. Karam; Mary E. Reyland
View articletitled, Tyrosine Kinase Inhibitors Protect the Salivary Gland from Radiation Damage by Inhibiting Activation of Protein Kinase C-δ
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Companion Diagnostics and Cancer Biomarkers

Optimization of RAS/BRAF Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer
Cristina Santos; Daniel Azuara; Rocio Garcia-Carbonero; Pilar Garcia Alfonso; Alfredo Carrato; Mª Elena Elez; Auxiliadora Gomez; Ferran Losa; Clara Montagut; Bartomeu Massuti; Valenti Navarro; Mar Varela; Adriana Lopez-Doriga; Victor Moreno; Manuel Valladares; Jose Luis Manzano; Jose Maria Vieitez; Enrique Aranda; Xavier Sanjuan; Josep Tabernero; Gabriel Capella; Ramon Salazar
View articletitled, Optimization of <em>RAS/BRAF</em> Mutational Analysis Confirms Improvement in Patient Selection for Clinical Benefit to Anti-EGFR Treatment in Metastatic Colorectal Cancer
Supplementary data
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Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation
John K. Simmons; Aleksandra M. Michalowski; Benjamin J. Gamache; Wendy DuBois; Jyoti Patel; Ke Zhang; Joy Gary; Shuling Zhang; Snehal Gaikwad; Daniel Connors; Nicholas Watson; Elena Leon; Jin-Qiu Chen; W. Michael Kuehl; Maxwell P. Lee; Adriana Zingone; Ola Landgren; Peter Ordentlich; Jing Huang; Beverly A. Mock
View articletitled, Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation
Supplementary data
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Models and Technologies

Modeling Therapy Resistance in BRCA1/2-Mutant Cancers
Amy Dréan; Chris T. Williamson; Rachel Brough; Inger Brandsma; Malini Menon; Asha Konde; Isaac Garcia-Murillas; Helen N. Pemberton; Jessica Frankum; Rumana Rafiq; Nicholas Badham; James Campbell; Aditi Gulati; Nicholas C. Turner; Stephen J. Pettitt; Alan Ashworth; Christopher J. Lord
View articletitled, Modeling Therapy Resistance in <em>BRCA1/2</em>-Mutant Cancers
Supplementary data
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Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient–Derived Xenografts
Nur-Afidah Mohamed Suhaimi; Wai Min Phyo; Hao Yun Yap; Sharon Heng Yee Choy; Xiaona Wei; Yukti Choudhury; Wai Jin Tan; Luke Anthony Peng Yee Tan; Roger Sik Yin Foo; Suzanne Hui San Tan; Zenia Tiang; Chin Fong Wong; Poh Koon Koh; Min-Han Tan
View articletitled, Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient–Derived Xenografts
Supplementary data
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  • Online ISSN 1538-8514
  • Print ISSN 1535-7163

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