Project title: Discover new treatments for carcinoid cancer and pancreatic neuroendocrine cancer
Matthew Kulke, MD Dana-Farber Cancer Institute
- Status: Completed
- Year(s): 2005
- Research Type: Translational
- Primary Tumor Site: Other
- Area of Inquiry: Signaling/drug targets
General Description
Dr. Kulke’s research focused on discovering new treatments for small intestine and pancreatic neuroendocrine tumors. Using a tumor database, Dr. Kulke analyzed genes and biological substances, such as hormones and cell proteins in patients, to link this information to disease occurrence and progression.
Results
Dr. Kulke and his team identified the DNA repair enzyme MGMT as a key predictor of neuroendocrine tumor response to alkylating agents, a class of chemotherapy. Characterized the mTOR signaling pathway in neuroendocrine tumors and found potential new therapeutic targets. Conducted many clinical trials, including those that have led to the FDA approval of two drugs, which are now used for the treatment of pancreatic neuroendocrine tumors. Continues to perform clinical trials using combination treatments, as well as a novel serotonin inhibitor drug for the treatment of carcinoid syndrome.
He characterized the mTOR signaling pathway in neuroendocrine tumors, identifying key downstream proteins that are activated and lead to adverse outcomes; these proteins may represent new therapeutic targets. He is currently exploring additional genetic and molecular predictors of both treatment outcome and of neuroendocrine tumor risk that should shed light on new pathways involved in neuroendocrine tumorigenesis, and lead to new therapeutic approaches.
Publications
Qian ZR, Ter-Minassian M, Chan JA, Imamura Y, Susanne M. Hooshmand, Kuchiba A, Morikawa T, Brais LK, Daskalova A, Heafield R, Lin X, Christiani DC, Fuchs CS, Ogino S, Kulke MH. Prognostic significance of mTOR pathway component expression in neuroendocrine tumors. J Clin Oncol. 2013 Sep 20; 31(27): 3418–3425. Published online 2013 Aug 26. doi: 10.1200/JCO.2012.46.6946
Chan JA, Kulke MH. Progress in the treatment of neuroendocrine tumors. Curr Oncol Rep. 2009 May;11(3):193-9.
Kulke MH, Hornick JL, Frauenhoffer C, Hooshmand S, Ryan DP, Enzinger PC, Meyerhardt JA, Clark JW, Stuart K, Fuchs CS, Redston MS. O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clin Cancer Res. 2009 Jan 1;15(1):338-45. doi: 10.1158/1078-0432.CCR-08-1476.
Kulke MH, Freed E, Chiang DY, Philips J, Zahrieh D, Glickman JN, Shivdasani RA. High-resolution analysis of genetic alterations in small bowel carcinoid tumors reveals areas of recurrent amplification and loss. Genes Chromosomes Cancer. 2008 Jul;47(7):591-603. doi: 10.1002/gcc.20561. PubMed PMID: 18383209.
Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J, Bergsland E, Stuart K, Tye L, Huang X, Li JZ, Baum CM, Fuchs CS. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol. 2008 Jul 10;26(20):3403-10. doi: 10.1200/JCO.2007.15.9020.
Kulke MH, Scherübl H. Accomplishments in 2008 in the management of gastrointestinal neuroendocrine tumors. Gastrointest Cancer Res. 2009;3(5 Supplement 2):S62-6.
Kulke, MH. Endocr Relat Cancer. Gastrointestinal neuroendocrine tumors: a role for targeted therapies? 2007 Jun;14(2):207-19.
Additional Details
- City: Boston
- State: Massachusetts
- Grant Duration: 5 years
- Awards: No information
DISCLAIMER
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.