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Suppression of Neuroendocrine Tumors via Epigenetic Regulation
Dr. Hua is one of the recipient's of the 2011 Caring for Carcinoid Foundation - AACR Grants for Carcinoid Tumor and Neuroendocrine Tumor Research. CFCF is pleased to announce the first cohort of winners of this award issued in partnership with the American Association for Cancer Research to: advance the understanding of neuroendocrine tumors; elucidate the mechanisms of currently available therapies; and identify new treatment targets for neuroendocrine tumors.
“This project suggests a novel treatment approach by targeting a new signaling pathway to treat carcinoid and neuroendocrine tumors. We are well-poised to…unravel the pathway as a new potential target to treat neuroendocrine cancers...” – Dr. Xianxin Hua
Dr. Hua’s lab has expertise in studying the function of oncogenes and tumor suppressor genes, including menin, a protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene. Patients with MEN1 syndrome have a mutation in the MEN1 gene.
Patients with MEN1 syndrome may develop pancreatic neuroendocrine and bronchial carcinoid tumors (among other tumors). We also know from other CFCF-funded research that sporadic pancreatic neuroendocrine tumors can have mutations in the MEN1 gene.
Dr. Hua’s lab has found that menin appears to suppress a pro-proliferative signaling pathway via protein methylation. Because menin mutations are linked to pancreatic neuroendocrine tumors, his findings suggest that targeting the menin-regulated signaling pathway may be crucial for treating neuroendocrine tumors. This goal of this project is to unravel the crucial role of the menin-regulated cascade in the maintenance of neuroendocrine tumors, underscoring the pathway as an important target for therapy.
By studying menin Dr. Hua seeks to uncover a new treatment strategy for patients with neuroendocrine tumors.
Abramson Cancer Research Institute, University of Pennsylvania
Xianxin Hua, MD, PhD
The goal of this proposal is to develop novel modalities that will be useful for treating pancreatic neuroendocrine tumors, by targeting the pathway that is regulated by menin, a tumor suppressor that is mutated in patients with the inherited Multiple endocrine neoplasia type I (MEN1) syndrome.
Carcinoid tumors and pancreatic neuroendocrine tumors pose serious threats as neoplastic diseases. Multiple Endocrine Neoplasia type I (MEN1) is a hereditary tumor syndrome including neuroendocrine tumors in several endocrine organs. With the grant support from CFCF, Dr. Xianxin Hua’s group has discovered that a menin mutation leads to an increase in Hedgehog signaling, a pro-proliferative and tumor-related pathway, via repression of a protein, PRMT5. Importantly, pharmacologic inhibition of Hedgehog signaling inhibits tumor cell growth. These findings thus uncover a new link between menin and Hedgehog signaling, and pave the way to conduct clinical trials to treat the neuroendocrine tumors using an already FDA approved drug.