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1 March 2024
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Raludotatug deruxtecan (R-DXd; DS-6000) is a CDH6-targeting antibody-drug conjugate (ADC) that was developed with DXd-ADC technology. Once R-DXd binds to and is internalized by CDH6-positive cancer cells, the TOP1 inhibitor DXd is released, leading to DNA damage and apoptosis. Further, the membrane permeability of released DXd allows it to penetrate neighboring cancer cells, even those that are CDH6-negative. See graphical abstract and read the full article on page 257. - PDF Icon PDF LinkTable of Contents
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ISSN 1535-7163
EISSN 1538-8514
Highlights
First Disclosure
Raludotatug Deruxtecan, a CDH6-Targeting Antibody–Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, Is Efficacious in Human Ovarian and Kidney Cancer Models
Hirokazu Suzuki; Shotaro Nagase; Chiemi Saito; Atsuko Takatsuka; Motoko Nagata; Kokichi Honda; Yuki Kaneda; Yumi Nishiya; Tomoyo Honda; Tomomichi Ishizaka; Kensuke Nakamura; Takashi Nakada; Yuki Abe; Toshinori Agatsuma
Review
Small Molecule Therapeutics
Palazestrant (OP-1250), A Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination
Alison D. Parisian; Susanna A. Barratt; Leslie Hodges-Gallagher; Fabian E. Ortega; Guadalupe Peña; Judevin Sapugay; Brandon Robello; Richard Sun; David Kulp; Gopinath S. Palanisamy; David C. Myles; Peter J. Kushner; Cyrus L. Harmon
Genetic Silencing of AKT Induces Melanoma Cell Death via mTOR Suppression
Gennie L. Parkman; Tursun Turapov; David A. Kircher; William J. Burnett; Christopher M. Stehn; Kayla O'Toole; Katie M. Culver; Ashley T. Chadwick; Riley C. Elmer; Ryan Flaherty; Karly A. Stanley; Mona Foth; David H. Lum; Robert L. Judson-Torres; John E. Friend; Matthew W. VanBrocklin; Martin McMahon; Sheri L. Holmen
Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma
Mason McCrury; Kennith Swafford; Sydnye L. Shuttleworth; Syed Hassan Mehdi; Baku Acharya; Debasmita Saha; Kevin Naceanceno; Stephanie D. Byrum; Aaron J. Storey; Ying-Zhi Xu; Claire Doshier; Vijay Patel; Ginell R. Post; Annick De Loose; Analiz Rodriguez; Leonard D. Shultz; Fenghuang Zhan; Donghoon Yoon; Brendan Frett; Samantha Kendrick
Large Molecule Therapeutics
Improving Intracellular Delivery of an Antibody–Drug Conjugate Targeting Carcinoembryonic Antigen Increases Efficacy at Clinically Relevant Doses In Vivo
Ian Nessler; Baron Rubahamya; Anna Kopp; Scott Hofsess; Thomas M. Cardillo; Nalini Sathyanarayan; Jennifer Donnell; Serengulam V. Govindan; Greg M. Thurber
Targeting Drug Resistance
ERBB4-Mediated Signaling Is a Mediator of Resistance to PI3K and BTK Inhibitors in B-cell Lymphoid Neoplasms
Alberto J. Arribas; Sara Napoli; Luciano Cascione; Laura Barnabei; Giulio Sartori; Eleonora Cannas; Eugenio Gaudio; Chiara Tarantelli; Afua A. Mensah; Filippo Spriano; Antonella Zucchetto; Francesca M. Rossi; Andrea Rinaldi; Manuel Castro de Moura; Sandra Jovic; Roberta Bordone Pittau; Anastasios Stathis; Georg Stussi; Valter Gattei; Jennifer R. Brown; Manel Esteller; Emanuele Zucca; Davide Rossi; Francesco Bertoni
Models and Technologies
Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers
Circulating Oncometabolite 2-hydroxyglutarate as a Potential Biomarker for Isocitrate Dehydrogenase (IDH1/2) Mutant Cholangiocarcinoma
Cha Len Lee; Grainne M. O'Kane; Warren P. Mason; Wen-Jiang Zhang; Pavlina Spiliopoulou; Aaron R. Hansen; Robert C. Grant; Jennifer J. Knox; Tracy L. Stockley; Gelareh Zadeh; Eric X. Chen
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NOTICE: This notice serves to inform the reader that, in 2023, AACR received a donation by Pfizer of the rights to royalties from the sale—within the United States—of Bavencio® (avelumab), a pharmaceutical owned by Merck. None of these funds are being, or will be, used to directly support any specific publication or author. If an individual article is published that deals with this particular drug, such article will include standard financial disclosures per AACR journal policy. For more detail regarding AACR’s established policies for authors, please go to https://aacrjournals.org/pages/editorial-policies#coi.
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