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Volume 19, Issue 3
1 March 2020
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    Cover Image

    issue cover
    Syk kinase has been well-described for its role in adaptive immunity and in this month's issue, Joshi and colleagues unveil its role in macrophage-driven immune suppression. In this cover image, a novel Syk inhibitor (SRX3188) docks into the active site of Syk kinase. SRX3188 forms hydrogen bonds with Ala451, Met450, and Arg498. Removal of a hydroxyl group improved the binding to PI3K, leading the authors to the chemotype of their dual Syk-PI3K inhibitor (SRX3207). By inhibiting the Syk-PI3K axis in tumors, the authors were able to generate anti-tumor immunity. Read the full article on page 755.
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ISSN 1535-7163
EISSN 1538-8514

Selected Articles from This Issue

Selected Articles from This Issue
View articletitled, Selected Articles from This Issue
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Small Molecule Therapeutics

Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas
Long-Sheng Chang; Janet L. Oblinger; Sarah S. Burns; Jie Huang; Larry W. Anderson; Melinda G. Hollingshead; Rulong Shen; Li Pan; Garima Agarwal; Yulin Ren; Ryan D. Roberts; Barry R. O'Keefe; A. Douglas Kinghorn; Jerry M. Collins
View articletitled, Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas
Supplementary data
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Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling
Sho Nakai; Hironari Tamiya; Yoshinori Imura; Takaaki Nakai; Naohiro Yasuda; Toru Wakamatsu; Takaaki Tanaka; Hidetatsu Outani; Satoshi Takenaka; Kenichiro Hamada; Akira Myoui; Nobuhito Araki; Takafumi Ueda; Hideki Yoshikawa; Norifumi Naka
View articletitled, Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling
Supplementary data
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Author Choice
Macrophage Syk–PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk–PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression
Shweta Joshi; Kevin X. Liu; Muamera Zulcic; Alok R. Singh; Dylan Skola; Christopher K. Glass; P. Dominick Sanders; Andrew B. Sharabi; Timothy V. Pham; Pablo Tamayo; Daniel Shiang; Huy Q. Dinh; Catherine C. Hedrick; Guillermo A. Morales; Joseph R. Garlich; Donald L. Durden
View articletitled, Macrophage Syk–PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk–PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression
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Tankyrase Inhibitors Target Colorectal Cancer Stem Cells via AXIN-Dependent Downregulation of c-KIT Tyrosine Kinase
Myung-Kyu Jang; Tetsuo Mashima; Hiroyuki Seimiya
View articletitled, Tankyrase Inhibitors Target Colorectal Cancer Stem Cells via AXIN-Dependent Downregulation of c-KIT Tyrosine Kinase
Supplementary data
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Preclinical Activity of Ribociclib in Squamous Cell Carcinoma of the Head and Neck
Gabrielle van Caloen; Sandra Schmitz; Mariama El Baroudi; Xavier Caignet; Sébastien Pyr dit Ruys; Pierre P. Roger; Didier Vertommen; Jean-Pascal Machiels
View articletitled, Preclinical Activity of Ribociclib in Squamous Cell Carcinoma of the Head and Neck
Supplementary data
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Large Molecule Therapeutics

Author Choice
Monoclonal Antibody Targeting Sialyl-di-Lewisa–Containing Internalizing and Noninternalizing Glycoproteins with Cancer Immunotherapy Development Potential
Silvana T. Tivadar; Richard S. McIntosh; Jia Xin Chua; Robert Moss; Tina Parsons; Abed M. Zaitoun; Srinivasan Madhusudan; Lindy G. Durrant; Mireille Vankemmelbeke
View articletitled, Monoclonal Antibody Targeting Sialyl-di-Lewis<sup>a</sup>–Containing Internalizing and Noninternalizing Glycoproteins with Cancer Immunotherapy Development Potential
Supplementary data
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Author Choice
Combination Immunotherapy with Cytotoxic T-Lymphocyte–Associated Antigen-4 and Programmed Death Protein-1 Inhibitors Prevents Postoperative Breast Tumor Recurrence and Metastasis
Ting Sun; Wenjia Zhang; Yuan Li; Zhengyu Jin; Yang Du; Jie Tian; Huadan Xue
View articletitled, Combination Immunotherapy with Cytotoxic T-Lymphocyte–Associated Antigen-4 and Programmed Death Protein-1 Inhibitors Prevents Postoperative Breast Tumor Recurrence and Metastasis
Supplementary data
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Site-Specific PEGylation of Anti-Mesothelin Recombinant Immunotoxins Increases Half-life and Antitumor Activity
Zeliang Zheng; Ryuhei Okada; Hisataka Kobayashi; Tadanobu Nagaya; Junxia Wei; Qi Zhou; Fred Lee; Tapan K. Bera; Yun Gao; William Kuhlman; Chin-Hsien Tai; Ira Pastan
View articletitled, Site-Specific PEGylation of Anti-Mesothelin Recombinant Immunotoxins Increases Half-life and Antitumor Activity
Supplementary data
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Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies
Binbin Xie; Jianqin Wan; Xiaona Chen; Weidong Han; Hangxiang Wang
View articletitled, Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies
Supplementary data
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Author Choice
Development of AO-176, a Next-Generation Humanized Anti-CD47 Antibody with Novel Anticancer Properties and Negligible Red Blood Cell Binding
Robyn J. Puro; Myriam N. Bouchlaka; Ronald R. Hiebsch; Benjamin J. Capoccia; Michael J. Donio; Pamela T. Manning; William A. Frazier; Robert W. Karr; Daniel S. Pereira
View articletitled, Development of AO-176, a Next-Generation Humanized Anti-CD47 Antibody with Novel Anticancer Properties and Negligible Red Blood Cell Binding
Supplementary data
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Cancer Biology and Translational Studies

Efficacy of FGFR Inhibitors and Combination Therapies for Acquired Resistance in FGFR2-Fusion Cholangiocarcinoma
Melanie A. Krook; Alexandria Lenyo; Max Wilberding; Hannah Barker; Mikayla Dantuono; Kelly M. Bailey; Hui-Zi Chen; Julie W. Reeser; Michele R. Wing; Jharna Miya; Eric Samorodnitsky; Amy M. Smith; Thuy Dao; Dorrelyn M. Martin; Kristen K. Ciombor; John Hays; Aharon G. Freud; Sameek Roychowdhury
View articletitled, Efficacy of FGFR Inhibitors and Combination Therapies for Acquired Resistance in FGFR2-Fusion Cholangiocarcinoma
Supplementary data
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Author Choice
Extracellular Vesicle–Mediated In Vitro Transcribed mRNA Delivery for Treatment of HER2+ Breast Cancer Xenografts in Mice by Prodrug CB1954 without General Toxicity
Alexis V. Forterre; Jing-Hung Wang; Alain Delcayre; Kyuri Kim; Carol Green; Mark D. Pegram; Stefanie S. Jeffrey; A.C. Matin
View articletitled, Extracellular Vesicle–Mediated <em>In Vitro</em> Transcribed mRNA Delivery for Treatment of HER2<sup>+</sup> Breast Cancer Xenografts in Mice by Prodrug CB1954 without General Toxicity
Supplementary data
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Phosphodiesterase 3A Represents a Therapeutic Target that Drives Stem Cell–like Property and Metastasis in Breast Cancer
Na Hao; Wenzhi Shen; Renle Du; Shan Jiang; Junyong Zhu; Yanan Chen; Chongbiao Huang; Yi Shi; Rong Xiang; Yunping Luo
View articletitled, Phosphodiesterase 3A Represents a Therapeutic Target that Drives Stem Cell–like Property and Metastasis in Breast Cancer
Supplementary data
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Targeting Phosphorylation of Y-Box–Binding Protein YBX1 by TAS0612 and Everolimus in Overcoming Antiestrogen Resistance
Tomohiro Shibata; Kosuke Watari; Akihiko Kawahara; Tomoya Sudo; Satoshi Hattori; Yuichi Murakami; Hiroto Izumi; Junji Itou; Masakazu Toi; Jun Akiba; Yoshito Akagi; Maki Tanaka; Michihiko Kuwano; Mayumi Ono
View articletitled, Targeting Phosphorylation of Y-Box–Binding Protein YBX1 by TAS0612 and Everolimus in Overcoming Antiestrogen Resistance
Supplementary data
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Targeting AXL and the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Melanoma
Karine Flem-Karlsen; Erin McFadden; Nasrin Omar; Mads H. Haugen; Geir Frode Øy; Truls Ryder; Hans Petter Gullestad; Robert Hermann; Gunhild Mari Mælandsmo; Vivi Ann Flørenes
View articletitled, Targeting AXL and the DNA Damage Response Pathway as a Novel Therapeutic Strategy in Melanoma
Supplementary data
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PIN1 Inhibition Sensitizes Chemotherapy in Gastric Cancer Cells by Targeting Stem Cell–like Traits and Multiple Biomarkers
Zhen-Zhen Zhang; Wei-Xing Yu; Min Zheng; Xin-Hua Liao; Ji-Chuang Wang; Da-Yun Yang; Wen-Xian Lu; Long Wang; Sheng Zhang; He-Kun Liu; Xiao Zhen Zhou; Kun Ping Lu
View articletitled, PIN1 Inhibition Sensitizes Chemotherapy in Gastric Cancer Cells by Targeting Stem Cell–like Traits and Multiple Biomarkers
Supplementary data
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Mechanisms of Entrectinib Resistance in a Neuroblastoma Xenograft Model
Suzanne P. MacFarland; Koumudi Naraparaju; Radhika Iyer; Peng Guan; Venkatadri Kolla; Yuxuan Hu; Kai Tan; Garrett M. Brodeur
View articletitled, Mechanisms of Entrectinib Resistance in a Neuroblastoma Xenograft Model
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Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers

Genetic Interactions and Tissue Specificity Modulate the Association of Mutations with Drug Response
Dina Cramer; Johanna Mazur; Octavio Espinosa; Matthias Schlesner; Daniel Hübschmann; Roland Eils; Eike Staub
View articletitled, Genetic Interactions and Tissue Specificity Modulate the Association of Mutations with Drug Response
Supplementary data
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Clinical Application of Next-Generation Sequencing–Based Panel to BRAF Wild-Type Advanced Melanoma Identifies Key Oncogenic Alterations and Therapeutic Strategies
Changhee Park; Miso Kim; Min Jung Kim; Hyeongmin Kim; Chan-Young Ock; Bhumsuk Keam; Tae Min Kim; Dong-Wan Kim; Jong-Il Kim; Dae Seog Heo
View articletitled, Clinical Application of Next-Generation Sequencing–Based Panel to <em>BRAF</em> Wild-Type Advanced Melanoma Identifies Key Oncogenic Alterations and Therapeutic Strategies
Supplementary data
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Genomic and Expression Analyses Define MUC17 and PCNX1 as Predictors of Chemotherapy Response in Breast Cancer
Waleed S. Al Amri; Lisa M. Allinson; Diana E. Baxter; Sandra M. Bell; Andrew M. Hanby; Stacey J. Jones; Abeer M. Shaaban; Lucy F. Stead; Eldo T. Verghese; Thomas A. Hughes
View articletitled, Genomic and Expression Analyses Define MUC17 and PCNX1 as Predictors of Chemotherapy Response in Breast Cancer
Supplementary data
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KLF4 p.A472D Mutation Contributes to Acquired Resistance to Cetuximab in Colorectal Cancer
Song Ye; Xiaoge Hu; Chao Ni; Weiwei Jin; Yaping Xu; Lianpeng Chang; Huaixiang Zhou; Jiahong Jiang; Liu Yang
View articletitled, <em>KLF4</em> p.A472D Mutation Contributes to Acquired Resistance to Cetuximab in Colorectal Cancer
Supplementary data
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Models and Technologies

Author Choice
Targeting Tumor Neoangiogenesis via Targeted Adenoviral Vector to Achieve Effective Cancer Gene Therapy for Disseminated Neoplastic Disease
Myungeun Lee; Zhi Hong Lu; Jie Li; Elena A. Kashentseva; Igor P. Dmitriev; Samir A. Mendonca; David T. Curiel
View articletitled, Targeting Tumor Neoangiogenesis via Targeted Adenoviral Vector to Achieve Effective Cancer Gene Therapy for Disseminated Neoplastic Disease
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