Publications by authors named "W H Zwart"
Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression.
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- - Phenotypic plasticity in cancer, particularly prostate cancer (PCa), leads to resistance against androgen receptor-targeted therapies, highlighting the need to understand its driving mechanisms to prevent resistance emergence.
- - The study found that loss of the tristetraprolin (TTP) gene (ZFP36) increases NF-κB activation, correlating with more aggressive disease and recurrence, especially when PTEN, another key driver in PCa, is also lost.
- - Targeting the NF-κB pathway with an inhibitor (DMAPT) showed promising therapeutic effects in tumors exhibiting co-loss of ZFP36 and PTEN, suggesting a potential new treatment strategy for castration-resistant PCa.
Article Synopsis
- Androgen receptor signaling inhibitors (ARSIs) have improved the treatment of metastatic castration-resistant prostate cancer (mCRPC), but many patients develop resistance to these therapies over time.
- Researchers analyzed genetic and transcriptomic changes in tumors before and after ARSI treatment to understand the underlying mechanisms of this resistance.
- They found that alterations enhancing androgen receptor signaling and low levels of somatostatin receptor 1 (SSTR1) are linked to reduced therapy effectiveness, suggesting that targeting SSTR1 could be a potential strategy to improve outcomes for mCRPC patients.
Article Synopsis
- The study explores how three-dimensional genomic structure variations impact gene expression and mutation rates in metastatic castration-resistant prostate cancer, using a combination of advanced sequencing techniques on 80 biopsy samples.
- Findings revealed significant differences in gene expression, methylation patterns, and structural variations between different chromatin compartments, along with specific chromatin contact loss at the AR locus linked to poor treatment responses.
- The research identified distinct subtypes of tumors based on their methylation and gene expression profiles, suggesting that DNA interactions could contribute to structural variant formation, ultimately enhancing understanding of tumor behavior and treatment outcomes.
Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26-27.
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