Objectives Treatment regimens in oncology frequently become personalized and multimodal. Therefore, reliable biomarkers to predict drug responses are needed. Here, we establish a functional assay reflecting response to DNA damage-based treatment approaches.

Methods Our Bimodal prediction of ovarian CAncer treatment REsponse (BCARE) score combines irradiation-induced DNA damage with functional assessment of homologous recombination (HR) DNA repair visualized by immunofluorescence detection of γH2AX and cyclinA2/RAD51 positive cells. BCARE is quantified by automated image analysis using Image J and R/Bioconductor. Treatment response of cancer cells to PARP inhibition, radiotherapy, and chemotherapy is analyzed by colony formation and MTT cell viability assays.

Results BCARE reflects the percentage of RAD51/cyclinA2 double positive cells. It significantly correlated with response to various drugs tested in 6 ovarian cancer cell lines: olaparib (R=0.92, p=0.0095), radiotherapy (R=0.78, p=0.0374), cisplatin (R=0.85, p=0.0325), doxorubicin (R=0.92, p=0.0095), and carboplatin (R=0.77, p=0.0738). Additionally, we show that the BCARE coincides with the cisplatin-resistant phenotype of A2780 cell line (BCARE A2780 3.3% versus 39% in A2780-cisplatin-resistant cells). The assay currently tests ex vivo patient derived cultures using a retrospective cohort of ovarian cancer patients. Correlations between BCARE scores and patient response to treatment will be investigated.

Conclusions Our BCARE-Score is capable of identifying dynamic alterations in HR-pathways as indicated by the differences observed in A2780 and cisplatin-resistant subline, which is not assessed by the current clinically applied HR assays. BCARE shows clear potential to be an effective tool in the prediction of primary drug response and more importantly in the detection of developed drug resistance.