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Genetics and biology of pancreatic ductal adenocarcinoma
Open accessAbstract
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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“the mutational frequency data combined with the observation from the simulations suggest that at least in the pancreatic cancer, where a KRAS mutation is a key initiator [68], a major shift in KRAS dynamics is not tolerated.”
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Metadata
- 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
- 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
- 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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