Novel Targets for Future Medical Treatments

There have been major developments in our understanding of the histopathological classification, genetics, molecular signaling pathways, and treatment of pNETs over the last decade. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is a promising target for well-differentiated pNETs. A number of agents targeting the vascular endothelial growth factor receptor (VEGF) have shown equal promise and success. The approval of both everolimus and sunitinib by the Food and Drug Administration (FDA) in 2011 for the treatment of progressive pNETs has forever changed the landscape of treatment of advanced pNETs. Each agent demonstrated an improvement in progression-free survival. Other novel therapies including bevacizumab, a vascular endothelial growth factor inhibitor, and insulin growth factor receptor inhibitors are showing promise with pNETs by improving progression-free survival alone or in combination with other targeted agents. There are an unprecedented number of ongoing clinical trials of innovative treatments for this disease and the development of combination therapy will lead to better therapeutic outcomes. Further advances are on the horizon.