Targeting the TGFβ pathway in uterine carcinosarcoma.

ABSTRACT: Uterine carcinosarcoma (UCS) is a relatively infrequent, but extremely aggressive endometrial malignancy. Although surgery and chemotherapy have improved outcomes, overall survival (OS) remains dismal due to the lack of targeted therapy and biphasic (epithelial and mesenchymal) nature that renders the tumor aggressive and difficult to manage. Here we report a role of transforming growth factor-β (TGFβ) in maintaining epithelial to mesenchymal transition (EMT) phenotype and aggressiveness in UCS. Using a 3D-culture system, we evaluated the efficacy of the transforming growth factor-β receptor-I (TGFβR1) kinase inhibitor Galunisertib (GLT), alone and in combination with standard chemotherapeutic drugs used for the management of UCS. We demonstrate that GLT by inhibiting canonical and non-can

SUBMITTER: Dwivedi SKD 

PROVIDER: S-EPMC7590842 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature