Pathologic Angiogenesis in Neuroendocrine Tumors

In recent years, a number of therapeutic agents have been tested in clinical trials and approved for neuroendocrine tumors (NETs), including an antiangiogenic agent (sunitinib) and an mTOR inhibitor (everolimus). Despite this clinical success, we still do not have biomarkers that can predict efficacy and provide clinically relevant information on potential resistance mechanisms against various antiangiogenic therapies (AA-Rxs). In order to address this important clinical challenge, there is an urgent need for pathologists to implement robust biomarker strategies to evaluate the expression of various members of the VEGF/VEGF receptor pathway and other relevant targets/biomarkers in human NET tissues. This will provide valuable biologic insights into pathologic angiogenesis, antiangiogenesis, and various resistance mechanisms in human NETs. Furthermore, selection of NET patients based on relevant biomarker or target expression in a given NET subtype will enable the current and emerging antiangiogenic therapies to be tailored to the right NET patients and will help achieve highest levels of clinical efficacy for these agents. An emerging approach to overcome resistance against AA-Rxs is concurrent targeting of VEGF and transcription factors or of multiple angiogenic pathways, such as VEGF and FGF.