Expression of antibody-drug conjugate targets in post-mortem samples of breast cancer metastases and normal tissue
While many Antibody Drug Conjugates (ADCs) are investigated in solid tumors, their target expression and heterogeneity is poorly documented in metastatic breast cancer. Here, we perform RNA sequencing to investigate expression of 72 ADC targets in 909 samples from 30 female patients from our post-mortem tissue donation program UPTIDER (NCT04531696). We report that the highest median expression in metastases is seen for FN1, MUC1, LAMP1, HER3 and SLC39A6. TROP2 and HER2 have the 9<sup>th</sup> and 27<sup>th</sup> highest expression. We observe reduced expression in metastases as compared to primary untreated tumors for 15 targets but observe only limited differences in expression between metastases of different subtypes. We show that TROP2, VTCN1, NECTIN4, HER2 and HER3 are interesting targets as they have higher mRNA expression in tumor as compared to normal tissues. This is confirmed at the protein level by explorative immunohistochemistry. Correlations between targets can help guide design of bispecific ADCs. Taken together, the results of this study can help inform the design and prioritization of drugs for the treatment of patients with metastatic breast cancer.
Authors
- Hava Izci (ORCID: https://orcid.org/0000-0002-3344-0198)
- Marion Maetens (ORCID: https://orcid.org/0000-0002-0505-2622)
- Anirudh Pabba (ORCID: https://orcid.org/0000-0003-2002-6956)
- Kevin Punie (ORCID: https://orcid.org/0000-0002-1162-7963)
- Josephine Van Cauwenberge (ORCID: https://orcid.org/0000-0001-9802-186X)
- Madita Nysen
- Evy Vanderheyden
- Elia Mario Biganzoli (ORCID: https://orcid.org/0000-0003-1202-5873)
- Christine Desmedt (ORCID: https://orcid.org/0000-0002-5223-5579)
- Ha Linh Nguyen
- Karen Van Baelen (ORCID: https://orcid.org/0000-0002-5700-3574)
- Gitte Zels (ORCID: https://orcid.org/0000-0002-6332-3830)
- D Lambrechts
- Giuseppe Floris (ORCID: https://orcid.org/0000-0003-2391-5425)
- K. Borremans
- F. Richard
- Bram Boeckx (ORCID: https://orcid.org/0000-0002-0296-6680)
- Thomas Van Brussel (ORCID: https://orcid.org/0000-0002-1706-8381)
- Wouter Van Den Bogaert (ORCID: https://orcid.org/0000-0002-5803-3409)
- Sigrid Hatse (ORCID: https://orcid.org/0000-0002-6764-2628)
- Amena Mahdami
- Françoise Derouane
- Sophia Leduc
- Patrick Neven
- Hans Wildiers
- Camille Carette
- Peter Vermeulen
Institutions
- University of Milan (IT)
- Breast Cancer Research Foundation (US)
- Universitair Ziekenhuis Leuven (BE)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Ziekenhuisnetwerk Antwerpen Stuivenberg (BE)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-26
- DOI
- https://doi.org/10.1038/s41467-025-67840-z
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Breast Cancer Research Foundation
- Breast Cancer Alliance
- American Society of Clinical Oncology
- Fonds Wetenschappelijk Onderzoek
- KU Leuven
- Vlaamse regering
- Universitaire Ziekenhuizen Leuven, KU Leuven