Download PDF
Horm Metab Res 2011; 43(12): 823-824
DOI: 10.1055/s-0031-1291328
Editorial
© Georg Thieme Verlag KG Stuttgart · New York

Neuroendocrine Neoplasms

M. Schott
1   Department of Endocrinology, Diabetes and Rheumatology, University Hospital, Düsseldorf, Germany
,
K. Öberg
2   Department of Medical Sciences, Division of Endocrine Oncology, Science for Life Laboratory, Uppsala University and Center of Excellence for Endocrine Tumors, University Hospital, Uppsala, Sweden
› Author Affiliations
Further Information

Publication History

received 12 October 2011

accepted 12 October 2011

Publication Date:
21 November 2011 (online)

Also available at
    Permissions and Reprints

Neuroendocrine neoplasms (NEN) appear homogeneous in terms of morphology, but constitute a very heterogeneous group of lesions in terms of biological and clinical features. Neuroendocrine neoplasms may occur in any organ, but are most commonly observed in the lung and the gastroenteropancreatic system (GEP). The aim of this Special Issue of Hormone and Metabolic Research is to give an overview on recent advances in the molecular understanding of NEN and also on clinical aspects of these tumors including new therapy strategies.

The European Neuroendocrine Tumor Society (ENETS) developed guidelines in the last 5 years to standardize and improve the diagnosis and therapy of GEP-NEN. Taking these guidelines into account, the TNM classification of the Union for International Cancer Control (UICC) was introduced in 2009. The new GEP-NEN classification of the World Health Organization (WHO) was presented 1 year later. The review article by Anlauf gives a beautiful overview on pathological aspects of the 2010 WHO classification of NEN [1]. The review article by Lindholm and Öberg adds more information as the article focuses on biomarkers and molecular imaging techniques, which are essential for the diagnosis and the follow-up of patients with NEN [2].

The paper by Pavel and Wiedenmann focuses on established therapies, which include somatostatin analogues and alpha-interferon, systemic chemotherapy, and loco-regional therapies of the liver for the treatment of NEN [3]. Importantly, the availability of novel agents and expression of targets, such as growth factor receptors, different subtypes of somatostatin receptors, and the mammalian target of rapamycin (mTOR) have led to the exploration of different classes of drugs and offer new treatment opportunities in NEN. Deutschbein and co-workers describe cytotoxic therapy of progressive undifferentiated NETs. The beneficial efficacy of a combination of cisplatinum and etoposide is reported [4].

The Special Issue also presents recent advances for the establishment of innovative therapies for the treatment of NEN. One of them is certainly the use of oncolytic viruses. Oncolytic viruses are emerging as anticancer agents, and they have also shown great promise for use against neuroendocrine tumors. Many viruses have a natural tropism for replication in tumor cells. Others can be genetically engineered to selectively replicate and kill tumor cells. Viruses have some advantages as therapeutic agents over current cytotoxic drugs and small molecules. They replicate in tumor cells and thereby increase in numbers over time leading to increased dosage. They are immunogenic and can alter the immunosuppressive tumor microenvironment and activate immune effector cells. They have also been shown to be able to kill drug resistant cancer stem cells. The review article by Essand and co-workers give an overview on the use for neuroendocrine tumors [5]. Another important issue in this context and also in the context of other immunological therapy approaches is the identification of tumor antigens recognized by the immune system. Thiel and co-workers present recent advances in this context [6]. The identification of antigens of NEN’s is essential for the development of directed immune therapies for these patients. Michael Culler reports on the development of new somatostatin-dopamine chimeras with approach to treatment of endocrine tumors including NEN [7].

Within this Special Issue some basic science papers were also included. One of them is the paper by Krausch et al. who focused on PTEN expression in pancreatic NEN [8]. PTEN is a well established tumor suppressor gene. It plays an important role in control of cell growth, apoptosis, cell adhesion, and cell migration. The authors could demonstrate a different PTEN expression in pancreatic NEN and this may therefore be helpful as a new prognostic factor for NEN. The same group also tested whether global histone modifications predict survival in organic hyperinsulinism and whether global histone modification pattern can be used to distinguish benign from malignant insulinoma [9]. The data presented revealed low K18 acetylation levels of histone H3 as independent prognostic factor in organic hyperinsulinism. This result warrants validation with independent data sets of organic hyperinsulinism, but is in line with several previous studies in different cancer entities. The broad applicability of this potential biomarker might lead to standardized diagnostic tests in near future and may help to manage insulinoma patients more effectively.

The group of Pietras report on the use of a mouse model of pancreatic NEN to find biomarkers of resistance to anti-angiogenic therapy [10]. Development of pericytes expressing alpha-smooth muscle actin as a biomarker indicates resistance to therapy with VEGF-receptor antibodies. Finally Krausch and co-workers describe a case of metachronous occurrence of a mature cystic teratomas and a well differentiated NET of the ileum (carcinoid) [11].