Abstract
Neuroendocrine neoplasms (NENs) constitute a heterogenous group of malignancies. Translational research into NEN cell biology is the cornerstone for drug development strategies in this field. Somatostatin receptor type 2 (SSTR2) expression is the hallmark of well-differentiated neuroendocrine tumors (NETs). Somatostatin analogs and peptide receptor radionuclide therapy (PRRT) form the basis of anti-SSTR2 treatment onto new combination strategies, antibody-drug conjugates and bispecific antibodies. Classical pathways involved in NET development (PI3K-Akt-mTOR and antiangiogenics) are reviewed but new potential targets for NET treatment will be explored. Epigenetic drugs have shown clinical activity in monotherapy and preclinical combination strategies are more than attractive. Immunotherapy has shown opposite results in different NEN settings. Although the NOTCH pathway has been targeted with disappointing results, new strategies are being developed. Finally, after years of solid preclinical evidence on different genetically engineered oncolytic viruses, clinical trials for refractory NET patients are now ongoing.
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