Project title: Exploring the role of epigenetic dysregulation in PanNET progression

Sita Kugel, PhD Fred Hutchinson Cancer Research Center

Sita Kugel, PhD
  • Status: Completed
  • Year(s): 2018
  • Grant Type: Pilot
  • Research Type: Basic
  • Primary Tumor Site: Pancreas
  • Area of Inquiry: Mapping NET dependencies

General Description

This one-year Pilot Project will investigate how pancreatic neuroendocrine tumors (PanNETs) spread to other organs in the body. Kugel and colleagues have found that a protein called SIRT6 plays a role in metastasis in PanNETs, in pre-clinical models. The investigators hypothesize that loss of SIRT6 may affect metastatic progression in PanNETs. To test this, they will block SIRT6 to see if tumor cells grow faster in its absence, which would suggest that SIRT6 may block metastasis. Their findings could inform the pursuit of targeted therapies, which could help stop the spread of PanNETs.



The purpose of this proposal was to understand the role of a gene called SIRT6 in the development of pancreatic neuroendocrine tumors (PanNETs). Our preliminary data showed that loss of this protein in mouse models leads to a more aggressive form of this disease suggesting that SIRT6 acts to prevent metastatic spread of this cancer.

We have found that SIRT6 may act in coordination with other genes that are commonly mutated in PanNETs such as DAXX. We are now working to understand how SIRT6 and DAXX may work together to prevent PanNET formation. In addition, we have gathered a large panel of PanNET tumor samples that were resected at an early or late stage (primary and metastatic tumors), which will allow us to understand how the expression of these proteins changes as tumors progress. Finally, we are building a new genetic mouse model of PanNET, which we believe will more closely reflect the human disease. Once it has been developed and characterized, this model system will be made available to the greater PanNET research community where it can be used for countless future studies.

Additional Details

  • City: Seattle
  • State: Washington
  • Grant Duration: 1 year
  • Awards: Pilot Project
  • Sponsor: Margie & Robert E. Petersen Foundation


NETRF funds laboratory research to understand the development of neuroendocrine tumors and translational research to explore new concepts in treatment. Research grant descriptions and research updates from NETRF are not intended to serve as medical advice. It can take years for research discoveries to be fully validated and approved for patient care. Always consult your health care providers about your treatment options.

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