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Abstract
Circulating tumor cells as a biomarker of response to treatment in patient derived xenograft mouse models of pancreatic adenocarcinoma
Highlights
Tumor cells that are present in peripheral circulation, or circulating tumor cells (CTCs), have been isolated from blood samples of patient’s with many solid cancers
While much work has been done to prove the prognostic value of CTC levels in breast, colorectal, prostate and lung cancers, little progress has been made in this area for pancreatic cancer due to the poor sensitivity of many CTC assays for patients with pancreatic ductal adenocarcinoma (PDAC) [1,2,3,4,5]
The highly sensitive microfluidic chip used in this study was capable of detecting and enumerating CTCs from only 250 mL of PDAC patient-derived xenograft (PDX) mouse blood
Summary
Tumor cells that are present in peripheral circulation, or circulating tumor cells (CTCs), have been isolated from blood samples of patient’s with many solid cancers These cells are an attractive target for staging and monitoring treatment effectiveness because they are obtained noninvasively through a routine blood draw and can be measured serially throughout the course of treatment. Promising therapies focus on targeting downstream effectors of Ras such as the Raf-MEK-ERK mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathways [10]. PI3K is an attractive therapuetic target as it is one of the main Ras effector signaling pathways, is involved in tumor growth and maintenance, and has been reported to be mutated in pancreatic cancers [11], [12], [13]. In vitro studies of various cancer cell lines have shown that BKM120 decreases phosporylated-Akt (p-Akt) levels, inhibits signaling pathways downstream of PI3K and p-Akt, and induces apoptosis [17]
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