Well-differentiated Pancreatic Neuroendocrine Tumors: from Genetics to Therapy

Overview

Journal Nat Rev Gastroenterol Hepatol

Specialty Gastroenterology

Date 2012 Feb 8

PMID 22310917

Citations 43

Authors

Roeland F de Wilde

Barish H Edil

Ralph H Hruban

Anirban Maitra

Affiliations

Soon will be listed here.

Abstract

Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ∼1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ∼65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance.

Citing Articles

The Role of Inositols in Endocrine and Neuroendocrine Tumors.

Mormando M, Puliani G, Bianchini M, Lauretta R, Appetecchia M Biomolecules. 2024; 14(8).

PMID: 39199391 PMC: 11353224. DOI: 10.3390/biom14081004.

Combined deletion of MEN1, ATRX and PTEN triggers development of high-grade pancreatic neuroendocrine tumors in mice.

Fuentes M, Lu X, Flores N, Hausmann S, Mazur P Sci Rep. 2024; 14(1):8510.

PMID: 38609433 PMC: 11014914. DOI: 10.1038/s41598-024-58874-2.

Angiopoietin-2 blockade suppresses growth of liver metastases from pancreatic neuroendocrine tumors by promoting T cell recruitment.

Lee E, OKeefe S, Leong A, Park H, Varadarajan J, Chowdhury S J Clin Invest. 2023; 133(20).

PMID: 37843277 PMC: 10575726. DOI: 10.1172/JCI167994.

Metabolic intervention by low carbohydrate diet suppresses the onset and progression of neuroendocrine tumors.

Chen Y, Yamamoto T, Takahashi Y, Moro T, Tajima T, Sakaguchi Y Cell Death Dis. 2023; 14(9):597.

PMID: 37679316 PMC: 10484927. DOI: 10.1038/s41419-023-06123-1.

Pancreatic cancer: Advances and challenges.

Halbrook C, Lyssiotis C, Pasca di Magliano M, Maitra A Cell. 2023; 186(8):1729-1754.

PMID: 37059070 PMC: 10182830. DOI: 10.1016/j.cell.2023.02.014.

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