Synergistic Analysis of Circulating Tumor Cells Reveals Prognostic Signatures in Pilot Study of Treatment-Naïve Metastatic Pancreatic Cancer Patients

SIMPLE SUMMARY: Pancreatic 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. ABSTRACT: 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.