New Targets for Antibody-Drug Conjugates in Metastatic Breast Cancer

In this video, Prof François Duhoux asks Dr Kristien Borremans to comment on the poster she presented at SABCS 2024: Expression of Antibody-Drug Conjugate targets in tumour and normal tissue from patients with metastatic breast cancer

The poster focuses on exploring new potential targets for ADCs in breast cancer treatment, building on the success of the three existing ADCs in this field. To identify these targets, researchers utilised samples from the Uptider post-mortem tissue donation program, which provided a range of tissues, including untreated primary samples, metastatic samples, and normal samples. Bulk mRNA sequencing was conducted on these samples to assess gene expression and identify promising targets.

Key findings revealed that traditional targets like HER2, HER3, and TROP2 were highly expressed in metastatic samples, validating their established roles in breast cancer therapy. However, other potential targets, such as VTCN1, were also identified. Interestingly, some of these targets showed high expression in both metastatic and normal samples, shedding light on potential off-target effects and the risk of tumour-related toxicity associated with certain therapies.

One of the most intriguing results was the lack of significant differences in target expression across various breast cancer subtypes. This included invasive lobular carcinoma versus mixed invasive breast carcinoma of no-special type metastases, as well as triple-negative breast cancer compared to hormone receptor-positive breast cancer. This uniformity in expression suggests that some targets might be broadly applicable across different subtypes of breast cancer.

Overall, the findings contribute another valuable dimension to the Uptider program and offer promising avenues for developing next-generation ADCs in breast cancer.