Servicenavigation

Project Details

Back

Projekt Print View

Role of Androgen Receptor Splice Variants in Development, Progression as well as Response to Treatment in Prostate Cancer

Subject Area Reproductive Medicine, Urology
Hematology, Oncology
Term from 2020 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 434121518
 
Final Report Year 2024

Final Report Abstract

The field of liquid biopsy can be used to obtain information about the disease in tumor patients. The detection of circulating tumor cells (CTC) in a patients blood is considered a biomarker for a more severe course of the disease. Truncated variants of the androgen receptor (AR), which is the main driver of prostate cancer (PC), are seen as candidates for predicting treatment success. AR splice variants (AR-V) are considered a resistance mechanism against AR-blocking therapies. ln an initial study, the presence of splice variant 7 (AR-V7) in CTC from patients was considered a biomarker for non-response. However, these results could not be clearly reproduced in follow-up studies. We analyzed the expression of AR full-length (AR-FL) and three commonly occurring AR-V. The expression of all ARs increased with disease progression, and the mRNA level of AR-FL was consistently higher than that of AR-V. CeII culture experiments then led us to hypothesize that treatment with ARTA increases the expression of the AR gene, resulting in the alternative AR-Vs. ln addition, we observed that AR-V status cannot predict treatment success for patients. Thus, the presence of AR-V alone does not seem to indicate resistance to ARTA. However, patients who were CTC-positive and AR-V-positive showed poorer overail survival. This result led to the question of which biomarker has the greater benefit for the prognosis of the disease: CTC or AR-V7. We compared both markers and found that the split by AR-V7 in the AR-V7-negative subgroup groups different patients together. This leads to a risk of not being able to monitor severe disease progression of patients to the best extent. We were able to show that AR-V is not predictive of a patients treatment success and is inferior to CTC status as a prognostic biomarker. ln another project, an attempt was made to establish cell lines as early research models from surgical material from localized PC patients. Unfortunately, no cell line could be established so far. However, we were able to transfer prostate epithelial cells into the cell culture and establish them. These will be used in future projects to simulate the development and early progression of PC in cell culture through genetic manipulation with known driver mutations of PC. ln the field of liquid biopsy, the most sensitive detection of biomarkers is of great clinical interest. ln our studies, however, we were able to identify a significantly higher group of biomarkerpositive patients than in comparative studies. Based on this, we carried out a comparative analysis of our detection method with the currently most common method. We were able to prove for both PC and other tumor entities (breast, lung) that our method detects a significantly higher number of biomarker-positive patients and thus has a higher sensitivity. The transfer of our method to liquid biopsy analysis would therefore mean improved patient characterization in terms of e.g. high-risk patients for the detection of CTC.

Publications

 
 

Additional Information

© 2026 DFG Disclaimer / Copyright / Privacy Policy

Textvergrößerung und Kontrastanpassung