Expression of antibody-drug conjugate targets in post-mortem samples of breast cancer metastases and normal tissue
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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 9th and 27th 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. Antibody drug conjugate (ADC) target expression beyond the traditional targets is poorly studied in metastatic cancer. Here, the authors analyse the expression of known and potential new ADC targets in normal and multi-organ metastatic samples of a post-mortem tissue donation program from patients with metastatic breast cancer.
Source: Nature Communications
Authors: Kristien Borremans, Anirudh Pabba, Gitte Zels, Amena Mahdami, Camille Carette, Marion Maetens, Karen Van Baelen, Josephine Van Cauwenberge, Ha Linh Nguyen, Hava Izci, Sophia Leduc, Sigrid Hatse, Madita Nysen, Bram Boeckx, Evy Vanderheyden, Thomas Van Brussel, Françoise Derouane, Kevin Punie, Wouter Van Den Bogaert, Peter Vermeulen, Elia Biganzoli, Diether Lambrechts, Patrick Neven, Hans Wildiers, Giuseppe Floris, François Richard, Christine Desmedt
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G4143201763, Breast cancer biology and ageing., G5048685634, LIQUIDEVO: Unravelling breast cancer heterogeneity, progression and treatment resistance in the context of a rapid post-mortem institutional tissue donation program using phylogenetic reconstruction algorithms and an Open Science approach., Atlas of therapeutic targets in metastatic breast cancer., Using standard and next-generation pathology to advance breast cancer characterization., Facing Adiposity in personalizing Treatment of Breast Cancer Patients
OpenAlex ID: W7117294594