Fig. 6
Treatment responses analyzed in BC-PDMs and identification of resistance and sensitivity marker panels. (A) Treatment response of breast cancer (BC) PDM to anti-cancer drugs. Microtumors were classified as “responder” and non-responder” based on the results of cytotoxicity measurements (Celltox Green™ assay; Promega). Cytotoxicity was determined in a time series (24 h, 48 h and 72 h). Treatment effects were analyzed as fold change of the respective control for each measurement time point using a mixed-effects model (REML) and Fisher’s uncorrected LST test. Statistically significant fold changes were defined as “response” and BC-PDMs were accordingly classified as “responders”. The numbers indicate BC sample number. (B-D) TAM, (E–H) DTX, (I-L) PTX and (M–O) PAB resistance and sensitivity marker panels. Median-centered, log2-transformed DigiWest AFI protein signals were compared between R and Non-R groups. Each data point within the scatter bar plots represents the same protein in R and Non-R. Lines connect protein data points between Non-R and R. Therapy resistance and sensitivity panels were identified including up to thirteen proteins (for detailed protein list see Table 1). Comparison of R and Non-R protein “panel” signals by non-parametric, unpaired Mann–Whitney U test. Within these protein panels individual, differentially expressed proteins are depicted (non-parametric, unpaired Mann–Whitney U test). *p < 0.05, **p < 0.01 and ***p < 0.001. Shown are mean with SEM. AFI: average fluorescent intensities; Non-R: non-responder; R: responder; TAM: tamoxifen (100 nM), DTX: docetaxel (5.5 µM), PTX: paclitaxel (4 µM), PAB: Palbociclib (150 nM)