Abstract
Simple SummaryPancreatic cancer is one of the most deadly cancer types because it usually is not diagnosed until the cancer has spread throughout the body. In this study, we isolate cancer cells found in the blood of pancreatic cancer patients called circulating tumor cells (CTCs) to study their mutation and gene expression profiles. Comparing patients with better and worse survival duration revealed signatures found in these cancer cells. Characterizing these signatures may help improve patient care by using alternative treatment options.Pancreatic ductal adenocarcinoma is typically diagnosed at late stages and has one of the lowest five-year survival rates of all malignancies. In this pilot study, we identify signatures related to survival and treatment response found in circulating tumor cells (CTCs). Patients with poor survival had increased mutant KRAS expression and deregulation of connected pathways such as PI3K-AKT and MAPK signaling. Further, in a subset of these patients, expression patterns of gemcitabine resistance mechanisms were observed, even prior to initiating treatment. This work highlights the need for identifying patients with these resistance profiles and designing treatment regimens to circumvent these mechanisms.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancer types, with a five-year survival rate of less than 3% in patients with advanced disease [1].Despite significant increases in survival rates of patients with other cancers, largely through early detection and the advent of targeted therapy, there has been only modest advancement in pancreatic cancer [2]
Panc-1 cells were grown in Dulbecco’s Modified Eagle’s Medium (DMEM)
All patients were diagnosed with metastatic, treatment-naïve PDAC (Table 2)
Summary
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly cancer types, with a five-year survival rate of less than 3% in patients with advanced disease [1]. Despite significant increases in survival rates of patients with other cancers, largely through early detection and the advent of targeted therapy, there has been only modest advancement in pancreatic cancer [2]. Current pancreatic cancer treatment options are mostly limited to chemotherapy, radiation, and surgery, or a combination of these approaches, with the exception of targeted and immunotherapies therapies in small number of patients with uncommon molecular alterations. The standard cytotoxic chemotherapy has modest clinical benefit along with a decrease in quality of life from potential side effects [7]. Patients with localized disease may be candidates for surgery, occasionally following upfront cytotoxic chemotherapy [7]
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