The antibody-drug conjugate sacituzumab govitecan (IMMU-132) represents a potential novel therapeutic strategy in cholangiocarcinoma

  • Mol Cancer Ther. 2025 Jun 13. doi: 10.1158/1535-7163.MCT-24-0972.
Racha Hosni  1 ,  Niklas Klümper  1 ,  Christine Sanders  1 ,  Sana Hosni  1 ,  Vittorio Branchi  1 ,  Alexander Semaan  2 ,  Abdullah Alajati  1 ,  Natalie Pelusi  3 ,  Susanna S Ng  4 ,  Damian J Ralser  1 ,  Saif-Eldin Abedellatif  3 ,  Hanno Matthaei  3 ,  Jörg Kalff  3 ,  Jasmitha Boovadira Poonacha  1 ,  Veronika Lukacs-Kornek  3 ,  Glen Kristiansen  1 ,  Maria A Gonzalez-Carmona  1 ,  Michael Hölzel  1 ,  Marieta I Toma  5
Affiliations
  • 1. University Hospital Bonn, Bonn, Germany.
  • 2. The University of Texas MD Anderson Cancer Center, United States.
  • 3. University Hospital Bonn, Germany.
  • 4. University Hospital Bonn, Bonn, 53127, Germany.
  • 5. University of Bonn, Bonn, Germany.
PMID: 40509933 DOI: 10.1158/1535-7163.MCT-24-0972
Abstract

Cholangiocarcinoma is a rare and aggressive Cancer type with limited therapeutic options. Several novel antibody-drug conjugates (ADCs) have demonstrated promising anti-tumor activity in solid tumors. This study aimed to investigate the expression and the potential prognostic role of the protein targets of the recently-developed ADCs, in cholangiocarcinoma. Moreover, the study aimed to establish patient-derived tumor organoids (PDOs) and to employ them for in vitro ADC testing. We evaluated the expression of TROP2, NECTIN4, folate receptor 1, HER2, and HER3 via immunohistochemistry (IHC) in a cholangiocarcinoma tissue microarray (TMA) (n=113) and analyzed the expression level with respect to clinico-pathological parameters. Furthermore, we generated cholangiocarcinoma PDO culture lines and used them to test the anti-tumor activity of ADCs in vitro. IHC analyses revealed that TROP2 was the most frequently expressed (91% of cases), followed by folate receptor 1 (51%), NECTIN4 (49%), HER3 (20%), and HER2 (7%). TROP2 showed moderate to high expression (H-score ≥100) in 74% of cases. No significant correlations with overall or disease-free survival, tumor grade, or tumor stage were observed. Six cholangiocarcinoma PDO lines were successfully established (55% success rate). All PDO lines expressed TROP2 concordantly with their parental tumors and showed growth-inhibition (IC50= 0.1 to 0.4 µg/mL) in response to sacituzumab govitecan (TROP2-targeting ADC). This study reveals that TROP2 is widely expressed in cholangiocarcinoma. Moreover, it provides preclinical evidence for the potential of use of sacituzumab govitecan as a novel therapeutic strategy in treating cholangiocarcinoma patients.

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