Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that originate from endocrine cells located in e.g. the pancreas, the thyroid and in the gastrointestinal and respiratory tract. These cells have ability to secrete a variety of metabolically active products including peptide hormones and amines, which cause specific clinical symptoms. As the majority of NETs grow slowly they are commonly diagnosed late, which involves a higher risk for metastatic disease, and a worse prognosis. Our work aims to improve the diagnostics, and to develop new treatments of NETs. We are also engaged in clinical trials to evaluate new treatments.
The neuroendocrine oncology group is part of the Centre of Excellence for Neuroendocrine Tumors at Uppsala University and Uppsala University Hospital, one of the world leading centers for diagnosis and treatment of neuroendocrine tumors. We are also part of U-CAN an initiative to build a biobank of blood and tumor samples from patients with different sorts of cancer. Our large collections of tumor samples and clinical data are of great importance for the different lines of research that we pursue.
Professor Eva Tiensuu Janson, MD, PhD, is the principal investigator of the Endocrine Oncology Group. She is the Dean of the Medical Faculty, member of the Executive Committee of the European Society for Neuroendocrine Tumors (ENETS) and chair of the Nordic Neuroendocrine Tumor Group (NNTG). The Endocrine Oncology Group also includes Staffan Welin, MD, PhD and head of the Clinical Endocrine Oncology Section at Uppsala University Hospital, Malin Grönberg, PhD and senior scientist at the research laboratory and PhD students Abir Ali, Ieva Lase and Clary Georgantzi. The research focuses on tumors derived from the small intestine, and studies e.g. the genetics of sporadic and familial NETs. In other projects the expression and clinical impact of neuroendocrine markers in neuroblastomas, breast cancer and small intestinal NETs are studied. Through the Nordic collaboration several projects directed towards neuroendocrine carcinomas are performed.
Projects, endocrine oncology
Genetics in familial and sporadic neuroendocrine tumors
Eva Tiensuu Janson, Malin Grönberg, Abir Ali and Staffan Welin
Small intestinal NETs (SI-NETs) have generally been considered a sporadic disease. We have now identified 20 Swedish families with an inherited variant of SI-NETs. We have performed exome and whole genome sequencing of familial and sporadic patients’ tumors and blood in order to define the specific genetic events which are involved in tumor development. This work is performed in collaboration with researchers at the department of immunology, genetics and pathology at Uppsala University (Professor Jan Dumanski). We have recently identified mutations in a group of genes which are potentially interesting as possible disease causing and we are now working to confirm this in a large cohort of more than 200 SI-NET patients. We are also expanding our material with families from Norway and Denmark.
Studies of neuroendocrine carcinomas (NEC)
Staffan Welin, Abir Ali, Malin Grönberg and Eva Tiensuu Janson
The Nordic NEC study has become highly recognized worldwide. The Nordic Neuroendocrine Tumor Group, led by Tiensuu Janson continues to perform research on this tumor group. In 2015 a group of international pathologists visited Uppsala to go through the tumor samples collected from patients in the Nordic NEC registry with the aim to develop a new classification. A clinical trial with a new combination of drugs (temozolomide and everolimus) for the subgroup of patients with a lower Ki67 has started and is recruiting patients from the Nordic countries. Further studies on this patient group are ongoing to evaluate the expression of tumor biomarkers in tissue and to evaluate the impact of surgery on survival for NEC patients.
Expression of neuroendocrine markers in tumors
Malin Grönberg, Clary Georgantzi, Abir Ali, Ieva Lase, Staffan Welin and Eva Tiensuu Janson
An area of interest is the expression of neuroendocrine biomarkers in cancer. Ghrelin expression was significantly correlated to better recurrence-free survival and breast cancer-specific survival. In related projects we have studied the expression of somatostatin receptors on neuroblastomas, and found frequent expression of these receptors, suggesting that treatment with somatostatin analogs should be further explored in neuroblastomas. Further studies of neuroendocrine markers in breast cancer, neuroblastomas and ACTH-producing NETs are ongoing.