Abstract IA25: Metastatic programs in pancreas cancer

The unusually high metastatic proclivity of pancreas cancer is life-limiting for a majority of patients including those treated at early stages. A minority of patients nevertheless presents with and succumbs to locally destructive disease. These distinct disease presentations and predilections for distant spread versus local growth of the primary tumor also suggest that the appropriate selection and application of systemic versus local therapies might increase their efficacy and prolong patient survival. We have undertaken a systematic effort to dissect the pathophysiologic mechanisms underlying the extreme lethality of pancreatic ductal adenocarcinoma (PDA) primarily through the generation and study of genetically engineered mouse models (GEMMs) of the disease. These models faithfully recapitulate the clinical syndrome, histopathology, molecular features and response and resistance to treatments seen in the human disease. We previously showed that point-mutant forms of Trp53 cooperate with oncogenic KrasG12D to promote widely metastatic disease in a GEMM of PDA. These and other studies have revealed that distinct combinations of tumor suppressor gene mutations can alter the pace, phenotype and prognosis of the resultant invasive disease initiated by oncogenic Kras. We have recently developed model systems that manifest the two ends of the disease phenotype described above and identified the Runx3/RUNX3 transcription factor as a master regulator of a metastatic program that d...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Niche / Cellular Interactions: Oral Presentations - Invited Abstracts Source Type: research