Developing novel treatments for NETs using CAR T-Cell Technology

Carl June, MD; Xianxin Hua, MD, PhD; David Metz, MD

Year: 2014
Institution: PA, Philadelphia, University of Pennsylvania
Country: United States
State: PA
Award Type: NETRF GRANTS 2005-2017
NET Type: Pancreas
Science Type: Translational

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.


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.


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.