The Caring for Carcinoid Foundation-AACR Grants for Carcinoid Tumor and Pancreatic Neuroendocrine Tumor Research represent a joint effort to promote and support innovative cancer research. These grants are available to independent junior and senior investigators to develop and study new ideas and approaches that have direct application and relevance to carcinoid tumors or pancreatic neuroendocrine tumors. Proposed research may be in any discipline of basic, translational, clinical or epidemiological cancer research. Applications are invited from researchers currently in the field as well as from investigators with experience in other areas of cancer research who have promising ideas or research approaches that can be applied to carcinoid tumor and pancreatic neuroendocrine tumor research.
2011 GRANTEES
Xanxin Hua, M.D., Ph.D. Associate Professor, University of Pennsylvania, Philadelphia, PA
Suppression of Neuroendocrine Tumors via Epigenetic Regulation
"We have found that menin appears to suppress the signaling pathway that is regulated by a hedgehog ligand. As the Hedgehog signaling pathway is often associated with enhanced proliferation and tumorigenesis in several tissues, and menin mutations are linked to pancreatic neuroendocrine tumors, our findings raise the possibility that targeting the Hedgehog signaling pathway may be crucial for treating neuroendocrine tumors. To test this hypothesis, we will first determine the role of Gas1, a molecule that is regulated by menin and is important for optimal Hedgehog signaling, in Hh signaling and beta cell proliferation. Second, we will examine the impact of inhibiting Hh signaling on beta cell proliferation and the pancreatic neuroendocrine tumors induced by menin inhibition excision. These studies will likely unravel the crucial role of Hh signaling in the maintenance of neuroendocrine tumors, underscoring the Hh signaling pathway as an important target for therapy against neuroendocrine tumors."
Top of Page
Charles M. Rudin, M.D., Ph.D.Professor, Johns Hopkins University, Baltimore, MD
Oncolytic Viral Therapy for Carcinoid and other Neuroendocrine Tumors
"My research group has focused on the development of novel cancer therapeutics, both in the laboratory and in the clinic. We have a particular interest in small cell lung cancer and other aggressive neuroendocrine cancers, including atypical carcinoid. Standard approaches to aggressive neuroendocrine cancers have changed minimally over the past 20 years. Novel therapeutic concepts are critically needed for these relatively rare but deadly cancers. My laboratory has been characterizing a novel picornavirus, SVV-001, which can selectively infect and destroy cancers with neuroendocrine differentiation. SVV-001 demonstrates a broad spectrum of activity against neuroendocrine tumors: about 50 percent of small cell carcinoma lines are permissive for the virus, as are a variety of other aggressive neuroendocrine cancers. The molecular and cellular determinants of SVV-001 permissivity have not been defined. We are seeking to identify the mechanisms of SVV-001 tumor cell entry as well as other cellular determinants of susceptibility to viral infection and lysis, using both innovative approaches and strategies that have been successfully used in defining the biology of other picornaviruses such as poliovirus. With the generous support of the Caring for Carcinoid Foundation and the American Association for Cancer Research, we will conduct a series of studies to define the basis of the selective tropism of SVV-001 for neuroendocrine tumors. These studies may identify biomarkers of viral permissivity, which will help guide subsequent clinical application of SVV-001 in patients with advanced neuroendocrine tumors. It is a terrific honor to receive this award in support of our work."
Top of Page