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Genes Dev. 2016 Feb 15;30(4):355-85. doi: 10.1101/gad.275776.115.

Genetics and biology of pancreatic ductal adenocarcinoma.

Author information

1
Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
2
Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
3
Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
4
Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;
5
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;
6
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.

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.

KEYWORDS:

KRAS; cancer metabolism; pancreatic cancer; tumor immune modulation

PMID:
26883357
PMCID:
PMC4762423
DOI:
10.1101/gad.275776.115
[Indexed for MEDLINE]
Free PMC Article

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