Establishment of drug sensitivity diagnostic assays

Breast cancer is a heterogeneous disease for which a multitude of chemotherapeutic agents with different mechanisms of action are available. In neo-adjuvant studies (PST) gene signatures predictive for drug cocktails have been described. However, since it is not clear which of the applied drugs exert the eventual anti-tumor effect, prediction with high accuracy remains a major challenge. In order to unravel response differences of individual drugs we combined gene expression profiling of primary tumor tissues with an in vitro drug sensitivity assay. Expression analysis of a small set of characteristic genes identified four major molecular breast cancer subclasses. Importantly, striking differences in sensitivity towards paclitaxel, epirubicin, 5-fluorouracil and carboplatin were observed between these molecular breast cancer subtypes.

The aim of our consortium is
i) to identify and if necessary to refine the expression signatures that predict chemosensitivity of primary tumour cells in vitro,
ii) to verify these expression signatures in a patient cohort receiving neoadjuvant chemotherapy,
iii) to develop and commercialize in vitro diagnostic kits based on mRNA expression analysis for the prediction of drug response.

Such new diagnostic tools will make outcome predictions more accurate, providing additional information that oncologists will use for treatment decisions.

Latest results can be found in detail in the descriptions of the subprojects