Abstract

This study was to clinically validate phosphorylated CDC2(pCDC2) as a biomarker for Wee1 kinase inhibitors by measuring pCDC2 in skin biopsies from patients receiving DNA damaging chemotherapy. Skin biopsies were performed at scheduled times after chemotherapy. Total CDC2 and pCDC2 in epidermal cells, hair follicle and bulb from skin biopsies were determined using chromogenic multiplex immunohis-tochemistry with multispectral image analysis. Statistical analyses were performed for each cell type after logtransformation of data. Thirty-one patients (29-88 years) completed the study. Significant induction of pCDC2 in response to chemotherapy was detected. Epidermis was most consistently evaluable across skin biopsies, demonstrating strong induction of pCDC2. The percentage of cells positive for total CDC2 and pCDC2 showed a 1.40-fold induction from baseline to 24h post-infusion (p=0.012) and a 2.05-fold increase from baseline to 48h (plt;0.001). The results suggest that pCDC2 may be used to assess the degree of Wee1 kinase inhibition in the chemotherapy setting. [Clinicaltrials.gov; NCT00800865]