PreprintCited by 533Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsCholangiocarcinoma and Gallbladder Cancer Studies

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Genetics and biology of pancreatic ductal adenocarcinoma

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Ying, Haoqiang, Dey, Prasenjit, Yao, Wantong, Kimmelman, Alec C., Draetta, Giulio F., Maitra, Anirban, DePinho, Ronald A.·2016·Genes & Development

DOI 10.1101/gad.275776.115

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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.

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Authors: Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Dana-Farber Cancer Institute (US)
ORCID: Ying, Haoqiang
Dey, Prasenjit
Yao, Wantong
Kimmelman, Alec C.
Draetta, Giulio F.
Maitra, Anirban
DePinho, Ronald A.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 2016-02-15
Volume: 30
Issue: 4
Pages: 355-385
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.275776.115
OpenAlex: W4295846302
Cited by: 527
References: 392
Citations by year: 2026: 20 · 2025: 33 · 2024: 44 · 2023: 68 · 2022: 56 · 2021: 75 · 2020: 57 · 2019: 48 · 2018: 51 · 2017: 59 · 2016: 16
Type: posted content
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Genes & Development (publishedVersion, cc-by-nc)
HighWire Press Open Archive (submittedVersion)
Funders: Sheikh Ahmed Center for Pancreatic Cancer Research
Pancreatic Cancer Moon Shot at the University of Texas MD Anderson Cancer Center
University of Texas Star Award (W81XWH-14-1-0429)
Department of Defense (U01DK108328, U01CA196403)
Odyssey Fellowship (Anne Eastland Spears Fellowship in GI Cancer Research)
University of Texas MD Anderson Cancer Center (RSG-13-298-01-TBG)
American Cancer Society (R01GM095567, R01CA157490, R01CA188048)
National Institutes of Health (14-90-25-DRAE, P01CA117969)
American Association for Cancer Research (W81XWH-11-1-0418)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
Keywords: pancreatic ductal adenocarcinoma, cancer genomics, molecular classification, cancer metabolism, DNA repair, tumor microenvironment, cancer immunotherapy, drug discovery, obesity, metabolic syndrome, preclinical models

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