Blair McNamara, Justin Harold, Diego Manavella, Stefania Bellone, Levent Mutlu, Tobias Max Philipp Hartwich, Margherita Zipponi, Yang Yang-Hartwich, Cem Demirkiran, Miguel Skyler Z Verzosa, Kevin Yang, Jungmin Choi, Weilai Dong, Natalia Buza, Pei Hui, Gary Altwerger, Gloria S Huang, Vaagn Andikyan, Mitchell Clark, Elena Ratner, Masoud Azodi, Peter E Schwartz, Elizabeth A Burton, Hiroaki Inagaki, Aaron Albers, Chao Zhang, Gideon Bollag, Joseph Schlessinger, Alessandro D Santin
INTRODUCTION: Uterine leiomyosarcomas (uLMS) are rare, highly aggressive tumors. Up to 30% of uLMS may harbor gain of function (GOF) in the MAP2K4 gene, important for tumor cell proliferation, differentiation and metastasis. We investigated the in vivo activity of a novel MAP2K4 inhibitor, PLX8725, against uLMS harboring MAP2K4 gene-amplification. METHODS: Two fully characterized uLMS (i.e., LEY-11 and LEY-16) were grafted into female CB-17/SCID mice. Treatments with control vehicle or PLX8725 (50 mg/kg) were given via oral gavage daily on weekdays for up to 60 days...
March 21, 2023: Gynecologic Oncology