TMPRSS2-ERG fusion

PARP inhibition with olaparib increased residual γH2AX/53BP1 foci post-irradiation in ERG+ cells, indicating enhanced radiosensitization...These findings suggest that ERG expression promotes dependency on PARP1-EJ, rendering ERG+ PCa more susceptible to PARP inhibition. Combining PARP inhibitors with RT may offer a tumor-selective radiosensitization for ERG+ PCa patients.

Certain immunohistochemical, radiological, and molecular parameters may be predictive of pathological upgrading in GG1 prostate cancer. Incorporation of these biomarkers into diagnostic evaluation and treatment planning may aid in refining risk stratification and avoiding overtreatment in clinically indolent cases. Although ADCtumor values were significantly associated with upgrading, their correlation with molecular markers such as PTEN, ERG, Ki-67, and TMPRSS2-ERG fusion were not statistically significant.

The TMPRSS2 rs12329760 T allele is associated with elevated prostate cancer risk and more severe clinicopathological features in Moroccan men. These findings highlight the potential prognostic relevance of the V160M variant and emphasize the need for further cellular and molecular studies to elucidate its functional role in AR signaling, TMPRSS2-ERG fusion biology, and ERG-related tumor aggressiveness. Such insights may contribute to the development of risk-stratified PCa management and tailored active surveillance strategies.

In conclusion, p53 staining was consistently associated with aggressive PCa and may serve as a reliable prognostic marker. High ETS2 expression correlates with delayed PSA recurrence in p53-negative tumors.

FOXA1 defines a major oncogenic axis in prostate cancer, distinct from TMPRSS2-ERG fusion and PROX1 induction. Class 1 and 2 FOXA1 mutations drive alternative transcriptional programs leading to therapy resistance, highlighting FOXA1 as a critical biomarker and target for chromatin-directed interventions.

Moreover, two clinical trials of neoadjuvant AR inhibition prior to radical prostatectomy showed greater increases in AKT activation in the T:E fusion-positive versus -negative tumors. These findings indicate that AKT activation may mitigate the efficacy of AR-targeted therapy in T:E fusion PCa and that these patients may most benefit from combination therapy targeting AR and AKT.

High level expression of GR is strongly linked to prostate cancer aggressiveness in uni- and multivariate analysis. GR immunohistochemistry - alone or in combination with other markers - holds great potential to identify patients with a high risk for tumor progression.

The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.

PROX1 expression is significantly associated with ERG expression and TMPRSS2-ERG fusion status in prostate cancer. These findings reinforce the role of PROX1 as an early marker and potential mediator of lineage plasticity. Targeting PROX1 or its regulatory pathways may offer a novel therapeutic strategy to mitigate plasticity-driven progression and treatment resistance in TMPRSS2-ERG fusion-positive prostate cancer.

To our knowledge, this is the first report that comprehensively evaluated the clonal origin of the rare prostate carcinosarcoma and characterized it using genomic and transcriptomic sequencing. It enhances our understanding of prostate cancer lineage plasticity and highlights the importance of developing novel therapies specifically targeted at prostate carcinosarcoma.

NGS on cytology material showed diagnostic and therapeutic utility in a subset of patients, with 10 of 46 patients (22%) having a change or potential in therapy based on NGS results.

ERG expression assessed by IHC was not associated with clinical outcomes in this population. These results do not support its role as a predictive biomarker in patients treated with CAB and RT. Further prospective studies are warranted to confirm these findings.