Use of microfluidics for 3D-culturing of patient-derived prostate cancer tissues and preclinical screening of personalized treatment strategies

• Applicant: Su Jung Oh-Hohenhorst, Ph.D.
• Subject Area: Reproductive Medicine, Urology ; Pathology ; Cell Biology
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 471209472

In recent years, the genomic and transcriptomic analysis of prostate cancer (PCa) enabled the identification of both, molecular alterations as well as novel pathways to target. However, the simultaneous translation of the new knowledge toward clinical implication has neither been successful nor led to significant changes of patient outcomes. This is due to the fact that currently available research models are insufficient for proof-of-concept testing of clinically highly variable PCa. To address these limitations, the "lap-on-chip" concept based on microfluidic systems has been developed. Patient-derived micro-dissected tumor (MDT) tissue is generated by 3D-culturing in a microfluidic device composed of several channels, which mirror the patient’s intra-tumor heterogeneity. Devices with parallel fluidic channels can trap multiple MDTs which can be incubated and treated with different therapeutics. Currently up to 32 MDTs can simultaneously be exposed to various therapeutic agents in one device, while the therapeutic response of the tissue is evaluated by specific assays. MDTs turned out to be an extremely powerful approach to study heterogeneity-related phenomena such as resistance or immune-based responses to treatment. Since this preclinical „on-chip" technology represents an in vivo-like model, it is a potential substitute for large animal experiments to prove therapeutic strategies. This project aims to utilize microfluidic devices for patient-relevant PCa research and high-throughput therapy screening within the meaning of personalized medicine. The microfluidic platform will facilitate direct drug testing on patient tissues obtained from radical prostatectomy or prostate biopsy. By refining patient stratification for clinical trials of novel treatments a maximum benefit for patients is expected. The main goals of this project include i) establishing the 3D-culturing of PCa cells from different origins in microfluidic devices; ii) utilizing the MDT chip technology to test different therapeutic strategies; and iii) analyzing molecular biological signatures of the tumors as well as revealing correlations with therapeutic responses.In summary we aim both, to establish a predicting test (“personalized drug screening”) for patients with high-risk or advanced prostate cancer undergoing surgery who need further (adjuvant) therapy as well as to identify possible predictive biomarkers for therapy response. In this regard, surgery could not only serve as an initial therapeutic approach but also as an effective acquisition of appropriate material from a donor tumor. The patient’s tissue can in turn be used to determine the biological behavior and drug-sensitivity prior to an initial adjuvant treatment. Furthermore, a microfluidic platform facilitates a quick as well as effective transfer of new findings from basic research into clinical evaluation.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Fred Saad