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Volume 20, Issue 12
1 December 2021
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    Dysregulation of PMRT5 occurs in various cancers, including lymphomas, lung cancers, and breast cancers. Due to the long residence binding time of JNJ-64619178, a novel PRMT5 inhibitor, the compound exhibits long-lasting target engagement that resists washout. JNJ-63619178 demonstrated potent anti-proliferative activity, supporting its continued clinical study. Read the full article on page 2317.
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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

Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Dirk Brehmer; Lijs Beke; Tongfei Wu; Hillary J. Millar; Christopher Moy; Weimei Sun; Geert Mannens; Vineet Pande; An Boeckx; Erika van Heerde; Thomas Nys; Emmanuel M. Gustin; Bie Verbist; Longen Zhou; Yue Fan; Vipul Bhargava; Pegah Safabakhsh; Petra Vinken; Tinne Verhulst; Angelique Gilbert; Sumit Rai; Timothy A. Graubert; Friederike Pastore; Danilo Fiore; Junchen Gu; Amy Johnson; Ulrike Philippar; Barbara Morschhäuser; David Walker; Desiree De Lange; Vikki Keersmaekers; Marcel Viellevoye; Gaston Diels; Wim Schepens; Jan Willem Thuring; Lieven Meerpoel; Kathryn Packman; Matthew V. Lorenzi; Sylvie Laquerre
View articletitled, Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Supplementary data
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Datopotamab Deruxtecan, a Novel TROP2-directed Antibody–drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells
Daisuke Okajima; Satoru Yasuda; Takanori Maejima; Tsuyoshi Karibe; Ken Sakurai; Tetsuo Aida; Tadashi Toki; Junko Yamaguchi; Michiko Kitamura; Reiko Kamei; Tomomichi Fujitani; Tomoyo Honda; Tomoko Shibutani; Sumie Muramatsu; Takashi Nakada; Riki Goto; Shu Takahashi; Miki Yamaguchi; Hirofumi Hamada; Yutaka Noguchi; Masato Murakami; Yuki Abe; Toshinori Agatsuma
View articletitled, Datopotamab Deruxtecan, a Novel TROP2-directed Antibody–drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells
Supplementary data
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Review

SMARCA4: Implications of an Altered Chromatin-Remodeling Gene for Cancer Development and Therapy
Kristina Mardinian; Jacob J. Adashek; Gregory P. Botta; Shumei Kato; Razelle Kurzrock
View articletitled, <em>SMARCA4</em>: Implications of an Altered Chromatin-Remodeling Gene for Cancer Development and Therapy
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Small Molecule Therapeutics

Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models
Katelyn F. Handley; Cristian Rodriguez-Aguayo; Shaolin Ma; Elaine Stur; Robiya Joseph; Emine Bayraktar; Santosh K. Dasari; Nghi Nguyen; Reid T. Powell; Mary Sobieski; Cristina Ivan; Mark Kim; Sujanitha Umamaheswaran; Deanna Glassman; Yunfei Wen; Paola Amero; Clifford Stephan; Robert L. Coleman; Yosef Landesman; Shannon N. Westin; Prahlad T. Ram; Anil K. Sood
View articletitled, Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models
Supplementary data
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Growth Inhibition and Induction of Innate Immune Signaling of Chondrosarcomas with Epigenetic Inhibitors
Tahir N. Sheikh; Xiao Chen; Xinjing Xu; John T. McGuire; Matthew Ingham; Chao Lu; Gary K. Schwartz
View articletitled, Growth Inhibition and Induction of Innate Immune Signaling of Chondrosarcomas with Epigenetic Inhibitors
Supplementary data
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Selectively Targeting Tumor Hypoxia With the Hypoxia-Activated Prodrug CP-506
Alexander M.A. van der Wiel; Victoria Jackson-Patel; Raymon Niemans; Ala Yaromina; Emily Liu; Damiënne Marcus; Alexandra M. Mowday; Natasja G. Lieuwes; Rianne Biemans; Xiaojing Lin; Zhe Fu; Sisira Kumara; Arthur Jochems; Amir Ashoorzadeh; Robert F. Anderson; Kevin O. Hicks; Matthew R. Bull; Maria R. Abbattista; Christopher P. Guise; Sofie Deschoemaeker; Sophie Thiolloy; Arne Heyerick; Morwena J. Solivio; Silvia Balbo; Jeff B. Smaill; Jan Theys; Ludwig J. Dubois; Adam V. Patterson; Philippe Lambin
View articletitled, Selectively Targeting Tumor Hypoxia With the Hypoxia-Activated Prodrug CP-506
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NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment
Tiange Dong; Priyal Dave; EunJeong Yoo; Brandon Ebright; Kabir Ahluwalia; Eugene Zhou; Isaac Asante; Malika Salimova; Hua Pei; Tracey Lin; Andrew Mead; Zeyang Li; Mark Humayun; Nicos A. Petasis; Alan L. Epstein; Stan G. Louie
View articletitled, NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment
Supplementary data
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A Benzenesulfonamide-Based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer
Fangfang Bi; Ziyan Jiang; Wonmin Park; Tobias M.P. Hartwich; Zhiping Ge; Kay Y. Chong; Kevin Yang; Madeline J. Morrison; Dongin Kim; Jaeyeon Kim; Wen Zhang; Liliia M. Kril; David S. Watt; Chunming Liu; Yang Yang-Hartwich
View articletitled, A Benzenesulfonamide-Based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer
Supplementary data
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Improving Theranostic Gallium-68/Lutetium-177–Labeled PSMA Inhibitors with an Albumin Binder for Prostate Cancer
Byoung Se Lee; Min Hwan Kim; So Young Chu; Woon Jung Jung; Hyeon Jin Jeong; Kyongkyu Lee; Hyeon Seok Kim; Mi Hyun Kim; Hee Seup Kil; Sang Jin Han; Yong Jin Lee; Kyo Chul Lee; Sang Moo Lim; Dae Yoon Chi
View articletitled, Improving Theranostic Gallium-68/Lutetium-177–Labeled PSMA Inhibitors with an Albumin Binder for Prostate Cancer
Supplementary data
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Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer
Ailed Cruz-Collazo; Jean F. Ruiz-Calderon; Hector Picon; Luis D. Borrero-Garcia; Irmaris Lopez; Linette Castillo-Pichardo; Maria del Mar Maldonado; Jorge Duconge; Julia I. Medina; Marvin J. Bayro; Eliud Hernández-O'Farrill; Cornelis P. Vlaar; Suranganie Dharmawardhane
View articletitled, Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer
Supplementary data
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Phosphoproteomics Identifies PI3K Inhibitor–selective Adaptive Responses in Pancreatic Cancer Cell Therapy and Resistance
Célia Cintas; Thibault Douche; Zahra Dantes; Emmanuelle Mouton-Barbosa; Marie-Pierre Bousquet; Coralie Cayron; Nicole Therville; Frédéric Pont; Fernanda Ramos-Delgado; Camille Guyon; Barbara Garmy-Susini; Paola Cappello; Odile Burlet-Schiltz; Emilio Hirsch; Anne Gomez-Brouchet; Benoît Thibault; Maximilian Reichert; Julie Guillermet-Guibert
View articletitled, Phosphoproteomics Identifies PI3K Inhibitor–selective Adaptive Responses in Pancreatic Cancer Cell Therapy and Resistance
Supplementary data
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Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations
Brion W. Murray; Evan Rogers; Dayong Zhai; Wei Deng; Xi Chen; Paul A. Sprengeler; Xin Zhang; Armin Graber; Siegfried H. Reich; Shanna Stopatschinskaja; Benjamin Solomon; Benjamin Besse; Alexander Drilon
View articletitled, Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations
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Large Molecule Therapeutics

IgE-Based Therapeutic Combination Enhances Antitumor Response in Preclinical Models of Pancreatic Cancer
Spas Dimitrov Markov; Thomas C. Caffrey; Kelly A. O'Connell; James A. Grunkemeyer; Simon Shin; Ryan Hanson; Prathamesh P. Patil; Surendra K. Shukla; Daisy Gonzalez; Ayrianne J. Crawford; Krysten E. Vance; Ying Huang; Kirsten C. Eberle; Prakash Radhakrishnan; Paul M. Grandgenett; Pankaj K. Singh; Ragupathy Madiyalakan; Tracy R. Daniels-Wells; Manuel L. Penichet; Christopher F. Nicodemus; Jill A. Poole; Elizabeth M. Jaffee; Michael A. Hollingsworth; Kamiya Mehla
View articletitled, IgE-Based Therapeutic Combination Enhances Antitumor Response in Preclinical Models of Pancreatic Cancer
Supplementary data
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Targeting the IGF-Axis Potentiates Immunotherapy for Pancreatic Ductal Adenocarcinoma Liver Metastases by Altering the Immunosuppressive Microenvironment
Masakazu Hashimoto; John David Konda; Stephanie Perrino; Maria Celia Fernandez; Andrew M. Lowy; Pnina Brodt
View articletitled, Targeting the IGF-Axis Potentiates Immunotherapy for Pancreatic Ductal Adenocarcinoma Liver Metastases by Altering the Immunosuppressive Microenvironment
Supplementary data
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Multimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199
Beatrice T. Wang; Tasnim Kothambawala; Ling Wang; Thomas J. Matthew; Susan E. Calhoun; Avneesh K. Saini; Maya F. Kotturi; Genevive Hernandez; Eric W. Humke; Marvin S. Peterson; Angus M. Sinclair; Bruce A. Keyt
View articletitled, Multimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199
Supplementary data
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Glypican-1 Is a Novel Target for Stroma and Tumor Cell Dual-Targeting Antibody–Drug Conjugates in Pancreatic Cancer
Shigehiro Tsujii; Satoshi Serada; Minoru Fujimoto; Sunao Uemura; Tsutomu Namikawa; Taisei Nomura; Ichiro Murakami; Kazuhiro Hanazaki; Tetsuji Naka
View articletitled, Glypican-1 Is a Novel Target for Stroma and Tumor Cell Dual-Targeting Antibody–Drug Conjugates in Pancreatic Cancer
Supplementary data
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Heme Sequestration as an Effective Strategy for the Suppression of Tumor Growth and Progression
Tianyuan Wang; Adnin Ashrafi; Purna Chaitanya Konduri; Poorva Ghosh; Sanchareeka Dey; Parsa Modareszadeh; Narges Salamat; Parinaz Sadat Alemi; Eranda Berisha; Li Zhang
View articletitled, Heme Sequestration as an Effective Strategy for the Suppression of Tumor Growth and Progression
Supplementary data
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Anti-VEGF Antibody Protects against Alveolar Exudate Leakage Caused by Vascular Hyperpermeability, Resulting in Mitigation of Pneumonitis Induced by Immunotherapy
Toshiki Iwai; Masamichi Sugimoto; Hina Patel; Keigo Yorozu; Mitsue Kurasawa; Osamu Kondoh
View articletitled, Anti-VEGF Antibody Protects against Alveolar Exudate Leakage Caused by Vascular Hyperpermeability, Resulting in Mitigation of Pneumonitis Induced by Immunotherapy
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Targeting Drug Resistance

Novel Mitochondria-Based Targeting Restores Responsiveness in Therapeutically Resistant Human Lung Cancer Cells
Liyuan Yin; Yi Zhang; Lijuan Yin; Yan Ou; Michael S. Lewis; Ruoxiang Wang; Haiyen E. Zhau; Qinghua Zhou; Leland W.K. Chung
View articletitled, Novel Mitochondria-Based Targeting Restores Responsiveness in Therapeutically Resistant Human Lung Cancer Cells
Supplementary data
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Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial
Javier Martin-Broto; Maria Lopez-Alvarez; David S. Moura; Rafael Ramos; Paola Collini; Cleofe Romagosa; Silvia Bagué; Salvatore L. Renne; Marta Barisella; Valerie Velasco; Jean-Michel Coindre; Daniel Lopez-Lopez; Joaquin Dopazo; Marco Gambarotti; Luca Braglia; Domenico Franco Merlo; Emanuela Palmerini; Silvia Stacchiotti; Vittorio L. Quagliuolo; Antonio Lopez-Pousa; Giovanni Grignani; Jean-Yves Blay; Antonella Brunello; Antonio Gutierrez; Claudia Valverde; Nadia Hindi; Angelo Paolo Dei Tos; Piero Picci; Paolo G. Casali; Alessandro Gronchi
View articletitled, Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial
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Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers

Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer
Yang Hu; Baraa K. Manasrah; Stephanie M. McGregor; Robert F. Lera; Roshan X. Norman; John B. Tucker; Christina M. Scribano; Rachel E. Yan; Mouhita Humayun; Kari B. Wisinski; Amye J. Tevaarwerk; Ruth M. O'Regan; Lee G. Wilke; Beth A. Weaver; David J. Beebe; Ning Jin; Mark E. Burkard
View articletitled, Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer
Supplementary data
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Monitoring Circulating Tumor DNA During Surgical Treatment in Patients with Gastrointestinal Stromal Tumors
Gustav Johansson; Marta Berndsen; Stefan Lindskog; Tobias Österlund; Henrik Fagman; Andreas Muth; Anders Ståhlberg
View articletitled, Monitoring Circulating Tumor DNA During Surgical Treatment in Patients with Gastrointestinal Stromal Tumors
Supplementary data
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Characterization of KRAS Mutation Subtypes in Non–small Cell Lung Cancer
Julia Judd; Nagla Abdel Karim; Hina Khan; Abdul Rafeh Naqash; Yasmine Baca; Joanne Xiu; Ari M. VanderWalde; Hirva Mamdani; Luis E. Raez; Misako Nagasaka; Sachin Gopalkrishna Pai; Mark A. Socinski; Jorge J. Nieva; Chul Kim; Antoinette J. Wozniak; Chukwuemeka Ikpeazu; Gilberto de Lima Lopes, Jr; Alexander I. Spira; W. Michael Korn; Edward S. Kim; Stephen V. Liu; Hossein Borghaei
View articletitled, Characterization of KRAS Mutation Subtypes in Non–small Cell Lung Cancer
Supplementary data
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Models and Technologies

Functional Characterization of Brain Tumor-Initiating Cells and Establishment of GBM Preclinical Models that Incorporate Heterogeneity, Therapy, and Sex Differences
Cesar A. Garcia; Adip G. Bhargav; Mieu Brooks; Paola Suárez-Meade; Sujan K. Mondal; Natanael Zarco; Karim ReFaey; Mark Jentoft; Erik H. Middlebrooks; Matija Snuderl; Anna Carrano; Hugo Guerrero-Cazares; Paula Schiapparelli; Rachel Sarabia-Estrada; Alfredo Quiñones-Hinojosa
View articletitled, Functional Characterization of Brain Tumor-Initiating Cells and Establishment of GBM Preclinical Models that Incorporate Heterogeneity, Therapy, and Sex Differences
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  • Online ISSN 1538-8514
  • Print ISSN 1535-7163

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