Cancer and Metastasis Reviews

, Volume 32, Issue 3, pp 465-477

First online:

The targeted therapy revolution in neuroendocrine tumors: in search of biomarkers for patient selection and response evaluation

  • Sara De DossoAffiliated withOncology Institute of Southern Switzerland
  • , Enrique GrandeAffiliated withRamón y Cajal University Hospital
  • , Jorge BarriusoAffiliated withLa Paz University Hospital
  • , Daniel CastellanoAffiliated withDoce de Octubre University Hospital
  • , Josep TaberneroAffiliated withVall d’Hebron University Hospital
  • , Jaume CapdevilaAffiliated withVall d’Hebron University HospitalDepartment of Medical Oncology, Vall d’Hebron University Hospital Email author 

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The molecular events of tumorigenesis in neuroendocrine tumors are poorly understood. Understanding of the molecular alterations will lead to the identification of molecular markers, providing new targets for therapeutics. The purpose of this review was to critically analyze the genetic abnormalities in neuroendocrine tumors, with the aim of identifying biomarkers that indicate a response to agents developed against these targets and to serve as an understanding for the combinations of different active compounds. Human epidermal growth factor receptor 1/2 (EGFR and HER2), vascular endothelial growth factor receptors, hepatocyte growth factor receptor (c-Met), platelet-derived growth factor receptor, insulin-like growth factor, phosphatidylinositol 3-kinase–Akt–mammalian target of rapamycin pathway, and heat shock proteins are all interesting candidate biomarkers with involvement in carcinogenesis and tumor evolution of several neoplasms, including neuroendocrine tumors. Some of them have already been evaluated both as targets and also as biomarkers in clinical trials conducted in advanced neuroendocrine tumor settings, and others should encourage further investigations into innovative therapeutic opportunities.


Neuroendocrine tumor Biomarker Target therapy Tyrosine kinase inhibitor