Abstract
BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection.DesignPatients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread.DiscussionPancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy.Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer.Trial registrationGerman Clinical Trials Register, DRKS00006179.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies
Design In this study we will analyze 4 biomarkers, two established proteins -CXCR4 and SMAD4- that are believed to be related to PDAC outcome and two new biomarkers derived from our own basic research -sex determining region Y-box 9 (SOX9) and Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)- that were already studied in a small group of patients
The PANCALYZE trail aims to predict the clinical course of pancreatic cancer on the basis of CXCR4, SMAD4, SOX9 and IFIT3 expression
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death in Germany and the incidence of PDAC increases constantly in most of the Western countries. The 5-year overall survival rate is around 6% making PDAC to one of the most lethal cancers of all known malignancies. Surgical resection remains the only potential curative treatment for PDAC raising the 5-year survival rate up to 14%. At the time of diagnosis less than 20% of the tumors are resectable while most are locally advanced or metastasized and inoperable. Despite adjuvant therapy almost 80% of all patients suffer from tumor recurrence within 2 years after resection. With a probability of 20% to 30% tumor recurrence is locally restricted whereas in the majority of patients the tumor systemically spreads to distant sites like liver and peritoneum [2, 3]
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