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Detecting expression of 5T4 in CTCs and tumor samples from NSCLC patients
Steven R Pirie-Shepherd1, Cory Painter1, Pamela Whalen1
1Pfizer Inc, WRD, EORCD, La Jolla, California, United States of America.
Abstract:
The fetal oncogene 5T4 is a cell surface protein, with overexpression observed in a variety of cancers as compared to normal adult tissue. The ability to select patients with tumors that express high levels of 5T4 may enrich a clinical trial cohort with patients most likely to respond to 5T4 targeted therapy. To that end, we developed assays to measure 5T4 in both tumors and in circulating tumor cells (CTCs). We identified the presence of 5T4 in both adenocarcinoma and squamous cell carcinoma of lung, in all clinical stages and grades of disease. CTCs were identified in peripheral blood from the majority of patients with NSCLC, and 5T4 was detectable in most samples. Although 5T4 was present in both CTCs and tumors in most patients, there was no concordance between relative amount in either sample type. Clinical response rates of patients treated with the therapies directed against 5T4 in early stage clinical trials, as determined by these assays, may provide important insights into the biology of 5T4 in tumors and the mechanisms of action of 5T4-targeting therapy.
Insights
The fetal oncogene 5T4 is overexpressed in many cancers. Assays were developed to detect 5T4 in lung tumors and circulating tumor cells (CTCs) for targeted therapy selection.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Diagnostics
Background:
- The 5T4 oncogene, a cell surface protein, is frequently overexpressed in various cancers compared to normal tissues.
- Targeted therapies against 5T4 show promise, but patient selection based on 5T4 expression is crucial for treatment efficacy.
Purpose of the Study:
- To develop and validate assays for measuring 5T4 protein levels in both primary tumors and circulating tumor cells (CTCs).
- To assess the presence and potential utility of 5T4 detection in non-small cell lung cancer (NSCLC) for patient stratification in 5T4-targeted therapies.
Main Methods:
- Development of specific assays to quantify 5T4 protein expression.
- Analysis of 5T4 presence in tumor tissue (adenocarcinoma and squamous cell carcinoma) and circulating tumor cells (CTCs) from NSCLC patients across different stages and grades.
- Comparison of 5T4 levels between tumor samples and CTCs.
Main Results:
- 5T4 was detected in both lung adenocarcinoma and squamous cell carcinoma across all clinical stages and grades.
- CTCs were identified in the majority of NSCLC patients, with detectable 5T4 in most CTC samples.
- No significant concordance was observed between the relative amounts of 5T4 in tumors and CTCs within the same patient.
Conclusions:
- The developed assays can detect 5T4 in NSCLC tumors and CTCs, supporting their potential use in patient selection for 5T4-targeted therapies.
- The lack of concordance between tumor and CTC 5T4 levels suggests independent biological significance and potential for complementary diagnostic information.
- Further clinical trials utilizing these assays are needed to correlate 5T4 expression with treatment response and elucidate 5T4-targeting therapy mechanisms.
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