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Volume 19, Issue 7
1 July 2020
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    Cover Image

    issue cover
    In this month's edition, Bennett and colleagues disclose BT5528, a Bicycle toxin-conjugate targeting EphA2. On the cover, BT5528 is shown bound to EphA2 on the surface of HT1080 fibrosarcoma cells in a High Content Screening assay. BT5528 provided persistent toxins to tumor cells while avoiding systemic exposure and has entered a Phase I clinical trial (NCT04180371). Read the First Disclosure on page 1385.
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ISSN 1535-7163
EISSN 1538-8514

Highlights

Selected Articles from This Issue
View articletitled, Selected Articles from This Issue
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MCT First Disclosures

Author Choice
MMAE Delivery Using the Bicycle Toxin Conjugate BT5528
Gavin Bennett; Amy Brown; Gemma Mudd; Philip Huxley; Katerine Van Rietschoten; Silvia Pavan; Liuhong Chen; Sophie Watcham; Johanna Lahdenranta; Nicholas Keen
View articletitled, MMAE Delivery Using the <em>Bicycle</em> Toxin Conjugate BT5528
Supplementary data
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Small Molecule Therapeutics

Author Choice
The Dysregulated Pharmacology of Clinically Relevant ESR1 Mutants is Normalized by Ligand-activated WT Receptor
Kaitlyn J. Andreano; Jennifer G. Baker; Sunghee Park; Rachid Safi; Sandeep Artham; Steffi Oesterreich; Rinath Jeselsohn; Myles Brown; Sarah Sammons; Suzanne E. Wardell; Ching-yi Chang; John D. Norris; Donald P. McDonnell
View articletitled, The Dysregulated Pharmacology of Clinically Relevant <em>ESR1</em> Mutants is Normalized by Ligand-activated WT Receptor
Supplementary data
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Combined Targeting of the BRD4–NUT–p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734
Chevaun D. Morrison-Smith; Tatiana M. Knox; Ivona Filic; Kara M. Soroko; Benjamin K. Eschle; Margaret K. Wilkens; Prafulla C. Gokhale; Francis Giles; Andrew Griffin; Bill Brown; Geoffrey I. Shapiro; Beth E. Zucconi; Philip A. Cole; Madeleine E. Lemieux; Christopher A. French
View articletitled, Combined Targeting of the BRD4–NUT–p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734
Supplementary data
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Perhexiline Demonstrates FYN-mediated Antitumor Activity in Glioblastoma
Shiva Kant; Pravin Kesarwani; Anthony R. Guastella; Praveen Kumar; Stewart F. Graham; Katie L. Buelow; Ichiro Nakano; Prakash Chinnaiyan
View articletitled, Perhexiline Demonstrates FYN-mediated Antitumor Activity in Glioblastoma
Supplementary data
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Author Choice
A Genome-scale CRISPR Screen Identifies the ERBB and mTOR Signaling Networks as Key Determinants of Response to PI3K Inhibition in Pancreatic Cancer
Charlotte K. Milton; Annette J. Self; Paul A. Clarke; Udai Banerji; Federica Piccioni; David E. Root; Steven R. Whittaker
View articletitled, A Genome-scale CRISPR Screen Identifies the ERBB and mTOR Signaling Networks as Key Determinants of Response to PI3K Inhibition in Pancreatic Cancer
Supplementary data
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Author Choice
Targeting the PI3K/AKT Pathway Overcomes Enzalutamide Resistance by Inhibiting Induction of the Glucocorticoid Receptor
Remi Adelaiye-Ogala; Berkley E. Gryder; Yen Thi Minh Nguyen; Aian Neil Alilin; Adlai R. Grayson; Wardah Bajwa; Keith H. Jansson; Michael L. Beshiri; Supreet Agarwal; Jose Antonio Rodriguez-Nieves; Brian Capaldo; Kathleen Kelly; David J. VanderWeele
View articletitled, Targeting the PI3K/AKT Pathway Overcomes Enzalutamide Resistance by Inhibiting Induction of the Glucocorticoid Receptor
Supplementary data
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Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma
Gireesh B. Reddy; David L. Kerr; Ivan Spasojevic; Artak Tovmasyan; David S. Hsu; Brian E. Brigman; Jason A. Somarelli; David Needham; William C. Eward
View articletitled, Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma
Supplementary data
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Rac Signaling Drives Clear Cell Renal Carcinoma Tumor Growth by Priming the Tumor Microenvironment for an Angiogenic Switch
Erik T. Goka; Pallavi Chaturvedi; Dayrelis T. Mesa Lopez; Marc E. Lippman
View articletitled, Rac Signaling Drives Clear Cell Renal Carcinoma Tumor Growth by Priming the Tumor Microenvironment for an Angiogenic Switch
Supplementary data
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Large Molecule Therapeutics

Inhibition of Tumor Cell Growth and Cancer Stem Cell Expansion by a Bispecific Antibody Targeting EGFR and HER3
Alexander Rau; Wolfgang S. Lieb; Oliver Seifert; Jonas Honer; Dennis Birnstock; Fabian Richter; Nadine Aschmoneit; Monilola A. Olayioye; Roland E. Kontermann
View articletitled, Inhibition of Tumor Cell Growth and Cancer Stem Cell Expansion by a Bispecific Antibody Targeting EGFR and HER3
Supplementary data
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Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers

Author Choice
Early Assessment of Molecular Progression and Response by Whole-genome Circulating Tumor DNA in Advanced Solid Tumors
Andrew A. Davis; Wade T. Iams; David Chan; Michael S. Oh; Robert W. Lentz; Neil Peterman; Alex Robertson; Abhik Shah; Rohith Srivas; Timothy J. Wilson; Nicole J. Lambert; Peter S. George; Becky Wong; Haleigh W. Wood; Jason C. Close; Ayse Tezcan; Ken Nesmith; Haluk Tezcan; Young Kwang Chae
View articletitled, Early Assessment of Molecular Progression and Response by Whole-genome Circulating Tumor DNA in Advanced Solid Tumors
Supplementary data
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A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Jing Yang; Kai Song; Wenbing Guo; Hailong Zheng; Yelin Fu; Tianyi You; Kai Wang; Lishuang Qi; Wenyuan Zhao; Zheng Guo
View articletitled, A Qualitative Transcriptional Signature for Predicting Prognosis and Response to Bevacizumab in Metastatic Colorectal Cancer
Supplementary data
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Cancer Biology and Translational Studies

Functional miRNA Screening Identifies Wide-ranging Antitumor Properties of miR-3622b-5p and Reveals a New Therapeutic Combination Strategy in Ovarian Tumor Organoids
Mégane Vernon; Bernard Lambert; Matthieu Meryet-Figuière; Emilie Brotin; Louis-Bastien Weiswald; Hippolyte Paysant; Nicolas Vigneron; Anaïs Wambecke; Edwige Abeilard; Florence Giffard; Marie-Hélène Louis; Cécile Blanc-Fournier; Pascal Gauduchon; Laurent Poulain; Christophe Denoyelle
View articletitled, Functional miRNA Screening Identifies Wide-ranging Antitumor Properties of miR-3622b-5p and Reveals a New Therapeutic Combination Strategy in Ovarian Tumor Organoids
Supplementary data
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EWS-FLI1–regulated Serine Synthesis and Exogenous Serine are Necessary for Ewing Sarcoma Cellular Proliferation and Tumor Growth
Sameer H. Issaq; Arnulfo Mendoza; Ria Kidner; Tracy I. Rosales; Damien Y. Duveau; Christine M. Heske; Jason M. Rohde; Matthew B. Boxer; Craig J. Thomas; Ralph J. DeBerardinis; Lee J. Helman
View articletitled, EWS-FLI1–regulated Serine Synthesis and Exogenous Serine are Necessary for Ewing Sarcoma Cellular Proliferation and Tumor Growth
Supplementary data
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A Novel Peptidylarginine Deiminase 4 (PAD4) Inhibitor BMS-P5 Blocks Formation of Neutrophil Extracellular Traps and Delays Progression of Multiple Myeloma
Marina Li; Cindy Lin; Hui Deng; Joann Strnad; Luca Bernabei; Dan T. Vogl; James J. Burke; Yulia Nefedova
View articletitled, A Novel Peptidylarginine Deiminase 4 (PAD4) Inhibitor BMS-P5 Blocks Formation of Neutrophil Extracellular Traps and Delays Progression of Multiple Myeloma
Supplementary data
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Author Choice
DCLK1-Isoform2 Alternative Splice Variant Promotes Pancreatic Tumor Immunosuppressive M2-Macrophage Polarization
Parthasarathy Chandrakesan; Janani Panneerselvam; Randal May; Nathaniel Weygant; Dongfeng Qu; William R. Berry; Kamille Pitts; Ben Z. Stanger; Chinthalapally V. Rao; Michael S. Bronze; Courtney W. Houchen
View articletitled, DCLK1-Isoform2 Alternative Splice Variant Promotes Pancreatic Tumor Immunosuppressive M2-Macrophage Polarization
Supplementary data
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Blockade of Cell Volume Regulatory Protein NKCC1 Increases TMZ-Induced Glioma Apoptosis and Reduces Astrogliosis
Lanxin Luo; Xiudong Guan; Gulnaz Begum; Dawei Ding; Jenesis Gayden; Md Nabiul Hasan; Victoria M. Fiesler; Jacob Dodelson; Gary Kohanbash; Baoli Hu; Nduka M. Amankulor; Wang Jia; Maria G. Castro; Baoshan Sun; Dandan Sun
View articletitled, Blockade of Cell Volume Regulatory Protein NKCC1 Increases TMZ-Induced Glioma Apoptosis and Reduces Astrogliosis
Supplementary data
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Pathway-Specific Genome Editing of PI3K/mTOR Tumor Suppressor Genes Reveals that PTEN Loss Contributes to Cetuximab Resistance in Head and Neck Cancer
Hiroki Izumi; Zhiyong Wang; Yusuke Goto; Toshinori Ando; Xingyu Wu; Xuefeng Zhang; Hua Li; Daniel E. Johnson; Jennifer R. Grandis; J. Silvio Gutkind
View articletitled, Pathway-Specific Genome Editing of PI3K/mTOR Tumor Suppressor Genes Reveals that <em>PTEN</em> Loss Contributes to Cetuximab Resistance in Head and Neck Cancer
Supplementary data
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