Discover New Treatments for Carcinoid Cancer and Pancreatic Neuroendocrine Cancer
Researcher: Matthew Kulke, MD Location: Dana-Farber Cancer Institute State: Massachusetts Year: 2005 Status: Finished
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To discover new treatments for carcinoid cancer and pancreatic neuroendocrine cancer.
Dr. Kulke’s research focuses on discovering new treatments for carcinoid and pancreatic endocrine tumors. Over the past two years, Dr. Kulke has created one of the country’s largest tumor databases for carcinoid and pancreatic endocrine cancer. Specifically, he has facilitated the collection of tumor specimens, blood and urine samples, and clinical data of carcinoid and pancreatic endocrine patients from all over the world.
With a research grant from the Caring for Carcinoid Foundation, Dr. Kulke is now leveraging this tumor database to undertake unprecedented research. Dr. Kulke is analyzing the genes and biologic substances, such as hormones and cell proteins, in carcinoid patients and linking this information to disease occurrence and progression. Specifically, Dr. Kulke is pursuing four lines of carcinoid research:
Identifying carcinoid risk factors
Evaluating prognostic indicators
Specifying therapeutic targets
Performing clinical trials
Dr. Kulke is taking many actions to complete these four lines of research. For example, he is working with scientists and technologies located at the Belfer Center for Cancer Genomics to clarify the genetic particularities of carcinoid tumors. To analyze the complex series of events that occur when a cell turns malignant, Dr. Kulke is using gene profiling technologies that perform this analysis not “one gene at a time”, but thousands of genes at a time. Dr. Kulke’s goal is to lead comprehensive, systematic, and ongoing genetic analyses of carcinoid tumors that will identify the specific genetic expressions associated with the various stages of tumor growth and generate the information required to develop novel, targeted therapies specifically for carcinoid patients.
Research Progress and 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.
Dr. Kulke is “grateful for the support we have received from the Foundation in our efforts to understand the biology of neuroendocrine tumors and develop new and better treatments for our patients.” In the past 10 years, his team has identified characteristic molecular alterations and predictors of treatment response in neuroendocrine tumors, and has played a leading role in the clinical development of novel therapeutic agents for this indication. He has recently established the Dana-Farber/Brigham and Women’s Program in Neuroendocrine and Carcinoid Tumors, which evaluates and treat approximately 200 new neuroendocrine tumor patients annually.
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.
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