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Pancreatic Cancer Action Network, AACR Fund Cancer Genomics Projects

NEW YORK (GenomeWeb News) – The Pancreatic Cancer Action Network and the American Association for Cancer Research have provided $400,000 to fund two researchers who are using genomic approaches to better understand and develop methods for combating pancreatic cancer.

The two new genomics-focused grants to investigators at the Translational Genomics Research Institute and the University of Pennsylvania are among a number of research projects that received nearly $5 million from PCAN and AACR this week, PCAN said on Tuesday.

At TGen, Associate Professor Michael Barrett was awarded $200,000 to study the genomic drivers of therapeutic responses in metastatic pancreatic cancer. Barrett, who is head of TGen's Oncogenomics Laboratory, is comparing tumor samples taken at the time when patients are first diagnosed to samples taken after they have undergone one or more treatments.

He and his colleagues have profiled 35 patients with metastatic pancreatic cancer in a phase II clinical trial sponsored by Stand Up To Cancer. They have generated genomic profiles of tumor populations in liver metastasis in each patient, and for 10 of these patients Barrett and his team had biopsy samples taken at the initial diagnosis. By comparing samples from two time points, Barrett and his team hope to provide a more dynamic view of tumor progression than studies based on tumor samples that were taken at only one time period. The aim of the project is to find out if clonal populations of tumor cells with distinct genetic changes that arise as disease progresses have an influence on how patients respond to treatment and to their general outcomes.

UPenn Assistant Professor Kathryn Wellen plans to use her $200,000 award to create a better picture of the metabolic control mechanisms at work in the pancreatic cancer cell epigenome. Recent evidence has shown that epigenetic modifications are regulated by cellular metabolites, and the most commonly mutated pancreatic cancer gene, KRAS, is thought to have an influence on metabolic pathways in cancer cells. Wellen and her research partners have already shown that the expression of mutant KRAS changes metabolite levels in pancreas cells. Now, Wellen plans to find out if mutant KRAS impacts the balance of cellular metabolites, altering the epigenetic state and facilitating the growth of tumor cells.

She and her colleagues plan to study the mechanisms linking KRAS activation to the regulation of histone acetylation, which has been shown to be affected by changes in the availability of one particular metabolite, acetyl-CoA. They aim to test the importance of KRAS-driven acetyl-CoA production and histone acetylation on gene expression, and the development and growth of tumors. The project could lead to new strategies that exploit the interactions between metabolism and epigenetics to target pancreatic cancer.