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Hedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)

ABSTRACT: This clinical trial is looking at the effect of a new drug called GDC-0449 in patients with cancer of the pancreas. Laboratory studies have shown that this drug blocks a process in pancreatic cells thought to be involved in cancer development and spread. This process is called the ‘Hedgehog signalling pathway’. As yet, it is unclear whether blocking hedgehog signalling will directly affect the tumour cells themselves or the surrounding normal tissue. Understanding this distinction will help improve treatment strategies for pancreatic cancer. Patients will be offered to participate in this research study if they have localised pancreatic cancer that can be removed by surgery. In the period between diagnosis and surgery the investigators do not normally treat patients, however in this trial the investigators will ask patients to take GDC-0449 during the approximately two weeks until the day of surgery. All patients that enter this study will have undergone a diagnostic biopsy of the pancreatic tumour and the investigators will collect a second sample of the tumour at surgery. The main question of this study is whether the investigators can detect a change in hedgehog signalling in the normal tumour surrounding tissue. Furthermore the investigators will look very carefully whether this treatment is safe for patients. All problems before and after surgery will be carefully documented and the investigators have defined strict rules to stop the study if the investigators observe serious problems.

DISEASE(S): Adenocarcinoma,Pancreatic Adenocarcinoma Resectable,Upper Gastro-intestinal Cancer,Pancreas,Pancreatic Ductal Adenocarcinoma,Cancer

PROVIDER: 2087072 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous cancer in which differences in survival rates might be related to a variety in gene expression profiles. Although the molecular biology of PDAC begins to be revealed, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Therefore, we performed microarray analyses on whole-tumour samples of 2 human PDAC subpopulations with similar clinicopathological features, but extremely distinct survival rates after potentially curative surgery, i.e., good outcome (OS and DFSM-bM-^@M-^I>M-bM-^@M-^I50M-bM-^@M-^Imonths) versus bad outcome (OSM-bM-^@M-^I<M-bM-^@M-^I19M-bM-^@M-^Imonths and DFSM-bM-^@M-^I<M-bM-^@M-^I7M-bM-^@M-^Imonths). Additionally, liver- and peritoneal metastases were analysed and compared to primary cancer tissue. The integrin and ephrin receptor families were upregulated in all PDAC samples, irrespective of outcome, supporting an important role of the interaction between pancreatic cancer cells and the surrounding desmoplastic reaction in tumorigenesis and cancer progression. Moreover, some components, such as ITGB1 and EPHA2, were upregulated in PDAC samples with a poor outcome, Additionally, overexpression of the non-canonical Wnt/M-NM-2-catenin pathway and EMT genes in PDAC samples with bad versus good outcome suggests their contribution to the invasiveness of pancreatic cancer, with M-NM-2-catenin being also highly upregulated in metastatic tissue. Thus, we conclude that components of the integrin and ephrin pathways and EMT-related genes might serve as molecular markers in pancreatic cancer as their expression seems to be related with prognosis. Microarray analysis was performed on 'Good' and 'Bad' patient samples (samples with similar pathological characteristics were chosen based on the definition of the 2 diverse survival outcome groups and the required RIN values above 7.1), on surrounding non-tumoural pancreatic control samples, liver metastasis (LM) and peritoneal metastasis (PM). Comparisons between good vs. control, bad vs. control, good vs. bad, and primary pancreatic cancer versus metastasis were performed.

Dataset Information

Hedgehog Inhibition for Pancreatic Ductal Adenocarcinoma (PDAC) in the Preoperative Setting (HIPPoS)

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