scholarly journals Her2 Expression in Circulating Tumor Cells Is Associated with Poor Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6014
Author(s):  
Denis Maillet ◽  
Nathalie Allioli ◽  
Julien Péron ◽  
Adriana Plesa ◽  
Myriam Decaussin-Petrucci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Her2 Status ◽  
Her2 Expression ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Psa Response

HER2−dependent signaling may support the development of metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling through ligand–independent mechanisms. From 41 mCRPC patients (including 31 treated with Androgen Receptor Signaling Inhibitors [ARSI]), Circulating Tumor Cells (CTCs) were prospectively enriched with AdnaTest platform and analyzed with a multiplexed assay for HER2 and AR-V7 mRNA expression. Then, we evaluated the impact of HER2 expression on PSA-response, Progression Free Survival (PFS) and Overall Survival (OS). HER2 expression was detected in CTCs of 26 patients (63%). Although PSA response was similar regardless of HER2 status, patients with HER2 positive CTCs had shorter PSA-PFS (median: 6.2 months versus 13.0 months, p = 0.034) and radiological-PFS (6.8 months versus 25.6 months, p = 0.022) than patients without HER2 expression. HER2 expression was also associated with a shorter OS (22.7 months versus not reached, p = 0.05). In patients treated with ARSI, multivariate analyses revealed that the prognostic impact of HER2 status on PSA-PFS was independent of AR-V7 expression and of the detection of CTCs by an AdnaTest. We showed for the first time the poor prognostic value of HER2 expression in CTCs from patients with mCRPC. The therapeutic interest of targeting this actionable pathway remains to be explored.

scholarly journals Role of Circulating Tumor Cells (CTC), Androgen Receptor Full Length (AR-FL) and Androgen Receptor Splice Variant 7 (AR-V7) in a Prospective Cohort of Castration-Resistant Metastatic Prostate Cancer Patients

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1365 ◽  
Author(s):  
Carlo Cattrini ◽  
Alessandra Rubagotti ◽  
Linda Zinoli ◽  
Luigi Cerbone ◽  
Elisa Zanardi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Splice Variant ◽  
Full Length ◽  
Lower Percentage ◽  
Castration Resistant ◽  
Psa Response ◽  
Androgen Receptor Splice Variant

Background: Circulating tumor cells (CTC), androgen receptor full-length (AR-FL), and androgen receptor splice variant 7 (AR-V7) are prognostic in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). AR-V7 seems to predict resistance to androgen-receptor signaling inhibitors (ARSi). Methods: We assessed the association of CTC, AR-FL, and AR-V7 with prostate-specific antigen (PSA) response and overall survival (OS). We used a modified AdnaTest CTC-based AR-FL and AR-V7 mRNA assay. Chi-square test, Fisher Exact test, Kaplan–Meier method, log-rank test, Cox proportional hazards models were used as appropriate. Results: We enrolled 39 mCRPC pts, of those 24 started a first-line treatment for mCRPC (1L subgroup) and 15 had received at least two lines for mCRPC (>2L subgroup). CTC, AR-FL, and AR-V7 were enriched in >2L compared to 1L subgroup. Detection of these biomarkers was associated with a lower percentage of biochemical responses. Only 1/7 AR-V7+ pts had a PSA response and received cabazitaxel. Median OS was 4.7 months (95% CI 0.6–8.9) in AR-V7+ pts and not reached in AR-V7− pts. AR-V7 was the only variable with prognostic significance in the Cox model. Conclusion: AR-V7, CTC, and AR-FL are associated with advanced mCRPC and AR-V7+ predicts for shorter OS.

scholarly journals Detection of Androgen Receptor Mutations in Circulating Tumor Cells in Castration-Resistant Prostate Cancer

2010 ◽  
Vol 56 (9) ◽  
pp. 1492-1495 ◽  
Author(s):  
Yuqiu Jiang ◽  
John F Palma ◽  
David B Agus ◽  
Yixin Wang ◽  
Mitchell E Gross
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Relative Abundance ◽  
Direct Sequencing ◽  
Receptor Gene ◽  
Missense Mutations ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

BACKGROUND Coding mutations in the AR (androgen receptor) gene have been identified in tissue samples from patients with advanced prostate cancer and represent a possible mechanism underlying the development of castration-resistant prostate cancer (CRPC). There is a paucity of tumor-derived tissue available for molecular studies of CRPC patients. Circulating tumor cells (CTCs) in the blood of CRPC patients represent a possible avenue for interrogating the disease of such patients. METHODS Circulating tumor cells were captured with the CellSearch® Circulating Tumor Cell (CTC) Kit and with the CellSearch Profile Kit plus Qiagen's AllPrep DNA/RNA Micro Kit for the measurement of the CTC count per 7.5 mL of blood and for the isolation of nucleic acids, respectively. The AR gene was amplified by the PCR, and mutation status and relative abundance were analyzed by applying Transgenomic's WAVE® denaturing HPLC technology followed by direct sequencing. RESULTS AR mutations were detected in 20 of 35 CRPC patients; 19 missense mutations, 2 silent mutations, 5 deletions, and 1 insertion were observed. The relative abundance of the mutants in the amplified products ranged from 5% to 50%. Many of the AR mutations were identified in surgical biopsies or at autopsy and were associated with resistance to androgen-directed therapies. CONCLUSIONS AR mutations can be identified in CTC-enriched peripheral blood samples from CRPC patients. This approach has the potential to open new perspectives in understanding CTCs and the mechanisms for tumor progression and metastasis in CRPC.

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