The Raymond and Beverly Sackler AACR Fellowships for Ileal Carcinoid Tumor Research are open to postdoctoral and clinical research fellows working at an academic, medical, or research institution who will be in the first 5 years of their postdoctoral training at the start of the grant term. 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 ileal carcinoid tumor research. Proposed research may be basic, translational, clinical, or epidemiological in nature and must have direct application and relevance to ileal carcinoid tumors.
2011 GRANTEES
Yanping Li, Ph.D.Postdoctoral Research Fellow, Oregon Health & Science University, Portland, OR
cAMP Regulation of Carcinoid Proliferation and Function
"Carcinoid tumors are composed of peptide- and amine-producing cells, which release hormones in response to signals from the nervous system. Our work has shown that hormonal elevation of cAMP can activate the MAP kinase cascade to stimulate cell growth in a wide range of cell types. Our recent research on the Epac family of guanine nucleotide exchangers suggests that Epac2 as a target of cAMP may be required for the secretion of hormones and peptides in carcinoid cells. The goal of the proposed research is to investigate whether there is a positive feedback between secretion and proliferation of carcinoid tumor cells. I will examine whether hormonal elevation of cAMP activates the MAP kinase cascade to stimulate carcinoid cell growth via the cAMP-dependent activation of the Rap1 guanine nucleotide exchanger Epac2, and whether cAMP-regulated secretion of hormones from carcinoid cells is medicated by Epac2. The Raymond and Beverly Sackler AACR Fellowship for Ileal Carcinoid Tumor Research will provide invaluable support for this project. We hope that our study would reveal the nature of this positive feedback loop in Carcinoid tumors and identify Epac2 as a novel target for anti-cancer therapeutics. I am honored to receive the AACR Fellowship. I would also like to thank my mentor Dr. Philip J. S. Stork for his support and guidance."
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Monica Ter-Minassian, Sc.D.Postdoctoral Fellow, Dana-Faber Cancer Institute, Boston, MA
Molecular Markers of Outcome in Ileal Carcinoid Tumor and other NET
"Neuroendocrine tumors (NETs) including ileal carcinoid are generally characterized by indolent course and the secretion of specific hormones. As these tumors progress, however, they may cause both morbidity and mortality from both overwhelming tumor burden and the overproduction of specific amines and peptides. The discovery and characterization of molecular and genetic prognostic factors has the potential to further improve the clinical management of patients with NET by providing markers of early detection and progression, and to identify patient subgroups that may be particularly responsive to targeted therapies.
The rarity of ileal carcinoid and other neuroendocrine tumors has presented a challenge in identifying clinical prognostic factors. Traditional prognostic factors such as tumor stage, histology and tumor grade have been validated in retrospective studies; however, few studies have evaluated these and other clinical variables in a prospective fashion. We aim to assess the prognostic value of these factors, together with the serologic biomarkers chromogranin A and alkaline phosphatase, in neuroendocrine tumor patients enrolled in a large, prospective outcomes study.
The role of common inherited genetic variation (single nucleotide polymorphisms, SNPs) as potential prognostic or predictive factors in ileal carcinoid and other NET remains completely unexplored. We, therefore, plan to evaluate SNPs in key molecular pathways implicated in ileal carcinoid and other neuroendocrine tumor growth, to identify variants associated with neuroendocrine tumor survival. We will further explore potential associations between these SNPs and treatment outcomes in metastatic patients treated with specific therapeutic agents. We specifically hypothesize that genetic variation in VEGFA, VEGFR1, VEGFR2 and other angiogenesis pathway genes is associated with treatment outcomes in patients treated with the vascular endothelial growth factor (VEGF) inhibitor bevacizumab, and that genetic variation in DNA repair genes, including MGMT and ERCC1, is associated with treatment outcomes in patients receiving treatment with temozolomide and other alkylating chemotherapy.
I am honored to be awarded this grant from the Raymond and Beverly Sackler AACR Fellowships for Ileal Carcinoid Tumor Research. I am excited to have the opportunity with this grant’s support to discover new and relevant molecular markers for ileal carcinoid survival and continue to develop a solid foundation as an independent researcher in this field. I am extremely grateful for the career guidance, excellent clinical and lab resources and support from my mentors Dr. Matthew Kulke and Dr. David Christiani on this project."
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