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Recent Advances in the Pathogenesis of Pancreatic Endocrine Neoplasms

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Mechanisms of Oncogenesis

Part of the book series: Cancer Growth and Progression ((CAGP,volume 12))

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Abstract

Evidence is rapidly accumulating to allow construction of a working hypothesis of the pathogenesis of PENs. Many studies have contributed significantly to our current understanding of PEN tumorigenesis and progression. We have learned, mainly through the study of β-cell regulation, that neogenesis and transdifferentiation, replication, hypertrophy, and apoptosis work together to control endocrine cell mass. However, the pluripotent stem cells thought to play a role in the neogenesis and transdifferentiation aree yet to be discovered. Studies have found many of the same mechanisms that operate during pancreatic development in the embryo, also regulate β-cell mass in adults. One could imagine how deregulation of these processes could lead to oncogenesis. All of these processes are steered by cell regulators such as glucose, c-Myc, P13K-AKT/PKB, PDX-1, Ngn-3, and others. Many of the members of these complex molecular pathways have been implicated in the pathogenesis of PENs. Genetic syndromes, which include PENs as one of their components, allow for the identification of genes associated with the genesis of PENs, including the MEN1 gene, vHL gene, NF-1 gene, TSC1 and TSC2 genes. Advanced molecular testing, is currently making it more feasible to pursue newer lines of genetic studies to unravel an increasing number of chromosomal aberrations associated with PENs. Multiple molecular alterations, involving migratory, cell cycle, and angiogenic functions, have been found to promote PEN development, growth, invasion, and metastases. As a result of these studies, phase III trials of novel therapies targeting cell regulators such as mTOR, VEGF and other targets are in progress. Focused investigation of various mediators/mechanisms implicated in the tumorigenesis of PENs will contribute to novel diagnostic, therapeutic, and preventive stratagies, as well as facilitate the development of prognostic and predictive markers, while continuing to advance our understanding of the pathogenesis of PENs.

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Acknowledgments

The authors would like to acknowledge the excellent assistance of Jean Stern, Mary Willis, LuAnn Ellsperman, and Rasa Hamilton.

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Authors and Affiliations

  1. Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Aejaz Nasir

  2. Anatomic Pathology, GI Tumor Program, Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Omie Mills & Aejaz Nasir

  3. Department of Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Nelly A. Nasir & Domenico Coppola

  4. Department of Anatomic Pathology, College of Medicine, University of South Florida, Tampa, FL, USA

    Nelly A. Nasir & Domenico Coppola

  5. Department of Pathology, Sir Mortimer Jewish General Hospital, McGill University, Montreal, CA, USA

    Nelly A. Nasir

  6. Neuroendocrine Cancer Research Divisions, GI Tumor Program,Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Jonathan R. Strosberg, Larry K. Kvols & Aejaz Nasir

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    Domenico Coppola

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Mills, O., Nasir, N.A., Strosberg, J.R., Kvols, L.K., Coppola, D., Nasir, A. (2010). Recent Advances in the Pathogenesis of Pancreatic Endocrine Neoplasms. In: Coppola, D. (eds) Mechanisms of Oncogenesis. Cancer Growth and Progression, vol 12. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3725-1_17

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