Dataset Information

Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.

ABSTRACT:

Background

Pancreatic adenocarcinoma (PDAC) remains a refractory disease; however, modern cytotoxic chemotherapeutics can induce tumor regression and extend life. A blood-based, pharmacogenomic, chemosensitivity assay using gene expression profiling of circulating tumor and invasive cells (CTICs) to predict treatment response was previously developed. The combination regimen of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel (G/nab-P) are established frontline approaches for treating advanced PDAC; however, there are no validated biomarkers for treatment selection. A similar unmet need exists for choosing second-line therapy.

Methods

The chemosensitivity assay was evaluated in metastatic PDAC patients presenting for frontline treatment. A prospective study enrolled patients (n = 70) before receiving either FOLFIRINOX or G/nab-P at a 1:1 ratio. Six milliliters of peripheral blood was collected at baseline and at time of disease progression. CTICs were isolated, gene-expression profiling was performed, and the assay was used to predict effective and ineffective chemotherapeutic agents. Treating physicians were blinded to the assay prediction results.

Results

Patients receiving an effective regimen as predicted by the chemosensitivity assay experienced significantly longer median progression-free survival (mPFS; 7.8 months vs. 4.2 months; hazard ratio [HR], 0.35; p = .0002) and median overall survival (mOS; 21.0 months vs. 9.7 months; HR, 0.40; p = .005), compared with an ineffective regimen. Assay prediction for effective second-line therapy was explored. The entire study cohort experienced favorable outcomes compared with historical controls, 7.1-month mPFS and 12.3-month mOS.

Conclusions

Chemosensitivity assay profiling is a promising tool for guiding therapy in advanced PDAC. Further prospective validation is under way (clinicaltrials.gov NCT03033927).

SUBMITTER: Yu KH

PROVIDER: S-EPMC10131181 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.

Yu Kenneth H KH Park Jennifer J Mittal Avni A Abou-Alfa Ghassan K GK El Dika Imane I Epstein Andrew S AS Ilson David H DH Kelsen David P DP Ku Geoffrey Y GY Li Jia J Park Wungki W Varghese Anna M AM Chou Joanne F-L JF Capanu Marinela M Cooper Brandon B Bartlett Andrew A McCarthy Devan D Sangar Vineet V McCarthy Brian B O'Reilly Eileen M EM

Cancer 20220601 15

<h4>Background</h4>Pancreatic adenocarcinoma (PDAC) remains a refractory disease; however, modern cytotoxic chemotherapeutics can induce tumor regression and extend life. A blood-based, pharmacogenomic, chemosensitivity assay using gene expression profiling of circulating tumor and invasive cells (CTICs) to predict treatment response was previously developed. The combination regimen of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel (G/nab-P) a ...[more]

PMID: 35647938

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Project description:Simple Summary Circulating tumor cells (CTCs) are important diagnostic and prognostic markers in cancer patients. However, current methods for isolating CTCs primarily focus on epithelial markers, such as EpCAM, leading to the underrepresentation of mesenchymal CTCs. This study proposes a novel method for continuous CTC isolation using magnetic nanoparticles coated with both EpCAM and vimentin antibodies, a mesenchymal marker. Using lateral magnetophoresis, the method demonstrated increased efficiency and reliability in isolating CTCs from patients with prostate (n = 17) and pancreatic (n = 5) cancer. Results indicated that using both EpCAM and vimentin antibodies significantly improved CTC isolation compared to using either marker alone, regardless of cancer stage. Abstract Circulating tumor cells (CTCs) display antigenic heterogeneity between epithelial and mesenchymal phenotypes. However, most current CTC isolation methods rely on EpCAM (epithelial cell adhesion molecule) antibodies. This study introduces a more efficient CTC isolation technique utilizing both EpCAM and vimentin (mesenchymal cell marker) antibodies, alongside a lateral magnetophoretic microseparator. The effectiveness of this approach was assessed by isolating CTCs from prostate (n = 17) and pancreatic (n = 5) cancer patients using EpCAM alone, vimentin alone, and both antibodies together. Prostate cancer patients showed an average of 13.29, 11.13, and 27.95 CTCs/mL isolated using EpCAM alone, vimentin alone, and both antibodies, respectively. For pancreatic cancer patients, the averages were 1.50, 3.44, and 10.82 CTCs/mL with EpCAM alone, vimentin alone, and both antibodies, respectively. Combining antibodies more than doubled CTC isolation compared to single antibodies. Interestingly, EpCAM antibodies were more effective for localized prostate cancer, while vimentin antibodies excelled in metastatic prostate cancer isolation. Moreover, vimentin antibodies outperformed EpCAM antibodies for all pancreatic cancer patients. These results highlight that using both epithelial and mesenchymal antibodies with the lateral magnetophoretic microseparator significantly enhances CTC isolation efficiency, and that antibody choice may vary depending on cancer type and stage.

Dataset Information

Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.

Background

Methods

Results

Conclusions

Publications

Circulating tumor and invasive cell expression profiling predicts effective therapy in pancreatic cancer.

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