Targeted Therapies

Coupled with our better understanding of our tumor biology and the development of new drugs, molecularly targeted drugs are now increasingly being used in the management of neuroendocrine neoplasms (NENs). The mammalian target of rapamycin (mTOR) inhibitor everolimus and the multiple tyrosine kinase inhibitor (TKI) sunitinib have been approved in progressive disease based on prolongation of progression-free survival in large placebo-controlled trials in pancreatic NET, and everolimus has also been shown to effective in other gastrointestinal and lung NETs. Many other targeted drugs such as tyrosine kinase inhibitors, vascular endothelial growth factor (VEGF) monoclonal antibodies, mTOR inhibitors, and epidermal growth factor receptor (EGFR) signaling inhibitors have been explored as single drugs or in combination with other drugs such as chemotherapeutics or somatostatin analogs. Recently, immune checkpoint inhibitors (ICIs) have also been started to test as a single agent or in combination with other ICI or targeted agents or with chemotherapy in clinical trials. Although minor responses, symptom control, and disease stabilization are common findings with prolonged progressive-free and overall survival, objective response rates are not high as that obtained with the current targeted drugs; therefore, efforts should continue to improve the outcome of the patients suffering from NETs.