Molecular Biology of Neuroendocrine Tumors

Neuroendocrine (NE), or carcinoid, tumors of the GI tract frequently metastasize. Surgery is often not possible for patients with advanced disease, and current therapies are ineffective for shrinking tumors and durable palliation of debilitating symptoms. Our lab and others have made significant advances in the understanding of the biology of NE tumors:

1. We have identified the Notch signaling pathway as an important regulator of NE tumor growth and hormone production. As a result, clinical trials of Notch activators are being evaluated in clinical trials for patients with advanced NE tumors
2. We have also found that a gene called Nkx2.2 is a critical regulator of normal endocrine cell development in the GI tract and is a novel diagnostic marker for GI NE tumors.
3. Progress in understanding GI NE tumor biology has been limited due to lack of models and cell lines necessary to study determinants of tumorigenesis. We have established novel GI NE tumor xenograft and cell lines, which will be important for the entire research community
4. In collaboration with Dr. Douglas Hanahan, we are conducting translational studies using targeted therapies for patients with advanced GI NE tumors. Recently , we  have identified collections of tiny molecules known as microRNAs that affect distinct processes critical for cancer progression. The findings help elucidate the important regulatory function of microRNAs in tumor biology. Recently, our lab helped validated the findings, which were based on an exquisite mouse model of pancreatic neuroendocrine tumors. Many of the same altered microRNAs in were found to be present in human pancreatic neuroendocrine tumors. This represents a major advance in our understanding of pancreatic neuroendocrine tumor biology, one that might be exploited to better treat patients.