Genetics and biology of pancreatic ductal adenocarcinoma

  1. Aram F. Hezel1,8,
  2. Alec C. Kimmelman1,3,8,
  3. Ben Z. Stanger5,
  4. Nabeel Bardeesy6, and
  5. Ronald A. DePinho1,2,4,7,9
  1. 1 Department of Medical Oncology, Dana-Farber Cancer Institute;
  2. 2 Department of Medicine, Brigham and Women’s Hospital;
  3. 3 Harvard Radiation Oncology Program;
  4. 4 Department of Genetics;
  5. 5 Gastrointestinal Unit,
  6. 6 Massachusetts General Hospital Cancer Center, Massachusettes General Hospital;
  7. 7 Center for Applied Cancer Science and Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
  1. 8

    8 These authors contributed equally to this work.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%–5%. The cancer’s lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biology and resistance to conventional and targeted therapeutic agents leads to a typical clinical presentation of incurable disease at the time of diagnosis. The well-defined serial histopathologic picture and accompanying molecular profiles of PDAC and its precursor lesions have provided the framework for emerging basic and translational research. Recent advances include insights into the cancer’s cellular origins, high-resolution genomic profiles pointing to potential new therapeutic targets, and refined mouse models reflecting both the genetics and histopathologic evolution of human PDAC. This confluence of developments offers the opportunity for accelerated discovery and the future promise of improved treatment.

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