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Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells
Published on: October 20, 2015
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Digital Circulating Tumor Cell Analyses for Prostate Cancer Precision Oncology
Ellen Heitzer1,2,3, Michael R Speicher4,2
1Institute of Human Genetics, Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, Graz, Austria.
Cancer Discovery
|March 4, 2018
Summary
This study developed a new method to detect prostate cancer markers in circulating tumor cells (CTCs). The RNA-based digital assay identifies patients with shorter survival and predicts disease spread in prostate cancer.
Area of Science:
- Oncology
- Molecular Diagnostics
- Prostate Cancer Research
Background:
- Accurate detection of prostate cancer progression and spread is crucial for effective treatment strategies.
- Circulating tumor cells (CTCs) offer a non-invasive window into tumor biology and patient prognosis.
- Existing methods for CTC analysis have limitations in sensitivity and specificity for key cancer-related transcripts.
Purpose of the Study:
- To adapt a microfluidic CTC isolation platform (CTC-iChip) with a digital RNA-PCR readout for prostate cancer.
- To develop RNA-based digital signatures for specific prostate cancer transcripts, including androgen receptor (AR) splice variant AR-V7 and TMPRSS2-ERG translocation.
- To evaluate the clinical utility of these RNA signatures in predicting outcomes for patients with metastatic castrate-resistant prostate cancer and localized disease.
Main Methods:
- Adaptation of the microfluidic CTC-iChip platform for isolation of CTCs.
- Integration of a digital RNA-polymerase chain reaction (dRNA-PCR) assay for quantification of specific RNA transcripts.
- Analysis of eight prostate-specific transcripts, including AR-V7 and TMPRSS2-ERG, in patient blood samples.
Main Results:
- RNA-based digital CTC signatures identified patients with metastatic castrate-resistant prostate cancer initiating first-line abiraterone therapy who had shorter overall survival.
- In patients with clinically localized prostate cancer, the identified signatures were associated with seminal vesicle invasion.
- The signatures also correlated with pelvic lymph node involvement in patients with localized disease.
Conclusions:
- The developed RNA-based digital CTC assay is a promising tool for prognostic stratification in prostate cancer.
- This method can identify patients at higher risk of poor outcomes in the metastatic setting.
- The assay also shows potential for predicting local disease spread in clinically localized prostate cancer.
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