Her2 Expression in Circulating Tumor Cells Is Associated with Poor Outcomes in Patients with Metastatic...

Area of Science:

• Oncology
• Molecular Biology
• Prostate Cancer Research

Background:

• HER2-dependent signaling may drive metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling.
• Understanding HER2's role in mCRPC progression is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the prognostic value of HER2 expression in circulating tumor cells (CTCs) of mCRPC patients.
• To evaluate the impact of HER2 expression on treatment response and survival outcomes.

Main Methods:

• Prospective enrichment of CTCs from 41 mCRPC patients using the AdnaTest platform.
• Multiplexed assay for HER2 and AR-V7 mRNA expression in CTCs.
• Evaluation of PSA response, Progression-Free Survival (PFS), and Overall Survival (OS) in relation to HER2 status.

Main Results:

• HER2 expression was detected in CTCs of 63% of patients.
• HER2-positive CTCs were associated with shorter PSA-PFS and radiological-PFS compared to HER2-negative.
• HER2 expression in CTCs showed a trend towards shorter Overall Survival (OS).
• In patients treated with Androgen Receptor Signaling Inhibitors (ARSI), HER2's prognostic impact on PSA-PFS was independent of AR-V7 expression.

Conclusions:

• HER2 expression in CTCs has a poor prognostic value in mCRPC.
• HER2 expression in CTCs is an independent prognostic marker for progression in mCRPC patients.
• Targeting HER2 in mCRPC warrants further investigation as a potential therapeutic strategy.