Abstract

Most precision cancer medicine efforts are based on the identification of oncogenic driver mutations by genome sequencing. We believe that this will miss therapeutic opportunities and additional profiling technologies as well as cell-based functional testing should be included. Our studies in leukemia indicate the value of ex vivo drug testing coupled with molecular profiling to identify novel, clinically actionable therapeutic opportunities in the patients. To establish this in solid tumors we have developed conditionally re-programmed, patient-derived cells (PDCs) from castration-resistant prostate cancer (CRPC), ovarian cancer (OvCa) and renal cell cancer (RCC). PDCs are compared with primary tumor tissue by genomic profiling and then subjected to drug sensitivity testing with 530 approved and investigational oncology drugs. Intra-patient heterogeneity can be assessed by multiple tumor samplings and healthy control cells enable identification of cancer cell specific drug responses. So far, our precision systems medicine approach has guided treatment of individual cancer patients. However, harmonization of and correlation of ex vivo and in vivo efficacies need to be demonstrated in large-scale clinical trials in the future. Our aim is to generate molecular profiles and drug testing data using representative PDCs from cancer patient samples to help clinicians in treatment decision and to facilitate the early selection of the best drug candidates for clinical development.