TROP2 expression and therapeutic targeting in uterine carcinosarcoma

Area of Science:

• Gynecologic Oncology
• Cancer Therapeutics
• Molecular Pathology

Background:

• Uterine carcinosarcoma (UCS) is a rare, aggressive endometrial carcinoma (EC) subtype.
• Novel therapeutic strategies are urgently needed for UCS treatment.
• TROP2 is an emerging target in various solid tumors.

Purpose of the Study:

• To evaluate TROP2 expression in UCS tissues.
• To assess the efficacy of TROP2 antibody-drug conjugate (ADC) targeting in patient-derived UCS models.
• To investigate sacituzumab govitecan (SG) as a potential therapy for UCS.

Main Methods:

• TROP2 protein and mRNA expression analyzed in 72 UCS tissues via immunohistochemistry and qRT-PCR.
• Nine patient-derived UCS organoid (PDO) models established and characterized.
• Efficacy of TROP2 ADC sacituzumab govitecan (SG) tested in UCS PDO and patient-derived xenograft (PDX) models.

Main Results:

• TROP2 expression detected in ≥90% of primary UCSs.
• UCS PDOs accurately reflected the molecular profiles of primary tumors.
• All UCS PDOs responded to SG, with significant tumor volume reduction in UCS PDX models.

Conclusions:

• The majority of UCSs exhibit detectable TROP2 expression.
• Sacituzumab govitecan demonstrates therapeutic potential in preclinical UCS models.
• Further investigation of TROP2 targeting is warranted for patients with UCS.