Pancreatic cancer has become the third leading cause of cancer-related death in the Western world despite advances in therapy of other cancerous lesions. Late diagnosis due to a lack of symptoms during early disease allows metastatic spread of the tumor. Most patients are considered incurable because of metastasized disease. On a cellular level, pancreatic cancer proves to be rather resistant to chemotherapy. Hence, early detection and new therapeutic targets might improve outcomes. The detection of DNA promoter hypermethylation has been described as a method to identify putative genes of interest in cancer entities. These genes might serve as either biomarkers or might lead to a better understanding of the molecular mechanisms involved. We checked tumor specimens from 80 patients who had undergone pancreatic resection for promoter hypermethylation of the zinc finger protein ZNF154. Then, we further characterized the effects of ZNF154 on cell viability and gene expression by in vitro experiments. We found a significant association between ZNF154 hypermethylation and better survival in patients with resectable pancreatic cancer. Moreover, we suspect that the cell growth suppressor SLFN5 might be linked to a silenced ZNF154 in pancreatic cancer.

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Background: The goal of this study was to assess the effect of combined radiochemotherapy in locally advanced and meta-static adenocarcinoma of the pancreas. Patients and Methods: 53 patients with pancreatic carcinoma were treated with combined radiochemotherapy. Radiotherapy was given as a split course of 24 Gy in two cycles for a total dose of 48 Gy. During the first 4 days of each course 1,000 mg 5-fluorouracil (5-FU)m₂/day were administered intravenously. Maintenance chemotherapy was continued with 5-FU (1,000 mg/m₂/day) until progression of disease. Results: The median survival time of the 53 patients treated, 29 thereof having metastatic disease, was 29 weeks. Partial remission was seen in 17% of the patients, 28% had stable disease and 55% tumor progression. Especially patients with partial remission or stable disease profited from combined modality treatment, resulting in a median survival time of 74 weeks and 41 weeks, respectively, in comparison to 18 weeks in patients with progressive disease. These results were highly significant. Treatment-related toxicity was moderate. 18 patients had WHO grade 3 and 4 toxicity, consisting of severe diarrhea and vomiting (13 patients) as well as moderate to severe leukocytopenia and hemorrhagic esopha-gitis. Conclusion: In this study only patients with partial response and stable disease profited from the combined radio-chemotherapy regimen. Partial response and stable disease occurred equally in patients with locally advanced and metastatic disease. Thus, patients with metastatic disease profited as much from therapy as patients with locally advanced cancer. Emphasis should focus on determining prognostic factors that could predict survival time prior to treatment initiation.