title: Genetics and biology of pancreatic ductal adenocarcinoma.
abstract: With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival.
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Ying
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Dey
authors.affiliation: Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
authors.forename: Wantong
authors.initials: W
authors.lastname: Yao
authors.affiliation: Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;
authors.forename: Alec C
authors.initials: AC
authors.lastname: Kimmelman
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Institute for Applied Cancer Science, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
authors.forename: Giulio F
authors.initials: GF
authors.lastname: Draetta
authors.affiliation: Department of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; Sheikh Ahmed Pancreatic Cancer Research Center, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; cancer metabolism; pancreatic cancer; tumor immune modulation