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Open AccessArticle

Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma

1
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
2
Weill Cornell Medical College, New York, NY 10065, USA
3
Adera Biolabs, Germantown, MD 20876, USA
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(12), 467; https://doi.org/10.3390/cancers10120467
Received: 5 September 2018 / Revised: 17 October 2018 / Accepted: 16 November 2018 / Published: 24 November 2018
(This article belongs to the Special Issue Circulating Tumor Cells (CTCs))
Previous studies have shown that pharmacogenomic modeling of circulating tumor and invasive cells (CTICs) can predict response of pancreatic ductal adenocarcinoma (PDAC) to combination chemotherapy, predominantly 5-fluorouracil-based. We hypothesized that a similar approach could be developed to predict treatment response to standard frontline gemcitabine with nab-paclitaxel (G/nab-P) chemotherapy. Gene expression profiles for responsiveness to G/nab-P were determined in cell lines and a test set of patient samples. A prospective clinical trial was conducted, enrolling 37 patients with advanced PDAC who received G/nab-P. Peripheral blood was collected prior to treatment, after two months of treatment, and at progression. The CTICs were isolated based on a phenotype of collagen invasion. The RNA was isolated, cDNA synthesized, and qPCR gene expression analyzed. Patients were most closely matched to one of three chemotherapy response templates. Circulating tumor and invasive cells’ SMAD4 expression was measured serially. The CTICs were reliably isolated and profiled from peripheral blood prior to and during chemotherapy treatment. Individual patients could be matched to distinct response templates predicting differential responses to G/nab-P treatment. Progression free survival was significantly correlated to response prediction and ΔSMAD4 was significantly associated with disease progression. These findings support phenotypic profiling and ΔSMAD4 of CTICs as promising clinical tools for choosing effective therapy in advanced PDAC, and for anticipating disease progression. View Full-Text
Keywords: circulating tumor and invasive cells; pancreatic cancer; SMAD4; gemcitabine; nab-paclitaxel; 5-fluorouracil; FOLFIRINOX circulating tumor and invasive cells; pancreatic cancer; SMAD4; gemcitabine; nab-paclitaxel; 5-fluorouracil; FOLFIRINOX
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Yu, K.H.; Ricigliano, M.; McCarthy, B.; Chou, J.F.; Capanu, M.; Cooper, B.; Bartlett, A.; Covington, C.; Lowery, M.A.; O’Reilly, E.M. Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma. Cancers 2018, 10, 467.

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