Genetics and biology of pancreatic ductal adenocarcinoma

被引:395
作者
Ying, Haoqiang [1 ]
Dey, Prasenjit [2 ]
Yao, Wantong [3 ]
Kimmelman, Alec C. [4 ]
Draetta, Giulio F. [1 ,3 ,5 ]
Maitra, Anirban [6 ,7 ]
DePinho, Ronald A. [2 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA
[4] Dana Farber Canc Inst, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Boston, MA 02115 USA
[5] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA
[6] Univ Texas MD Anderson Canc Ctr, Dept Pathol & Translat Mol Pathol, Houston, TX 77030 USA
[7] Univ Texas MD Anderson Canc Ctr, Sheikh Ahmed Pancreat Canc Res Ctr, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
KRAS; cancer metabolism; pancreatic cancer; tumor immune modulation; REGULATORY T-CELLS; MYELOID SUPPRESSOR-CELLS; TUMOR-INFILTRATING MACROPHAGES; NEOPLASTIC PRECURSOR LESIONS; PAPILLARY MUCINOUS NEOPLASM; COLONY-STIMULATING FACTOR; RAS-DRIVEN TUMORIGENESIS; K-RAS; ONCOGENIC KRAS; INTRAEPITHELIAL NEOPLASIA;
D O I
10.1101/gad.275776.115
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:355 / 385
页数:31
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