title: Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine.
abstract: Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis despite new treatments; approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and have identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but are now considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted approaches in PDA therapy.
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: erik.knudsen@utsouthwestern.edu.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Knudsen
authors.affiliation: Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
authors.affiliation: Department of Surgery, Jefferson Pancreatic, Biliary, and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.affiliation: Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: agnes.witkiewicz@utsouthwestern.edu.
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000628:therapy; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis
keywords: Kras; Myc; Notch; Smad4