Current and Emerging Therapies in Neuroendocrine Tumors: Impact of Genetic Targets on Clinical Outcomes
Monika Joshi, Zhaohai Yang, Harold Harvey, Chandra Belani and Nelson S. Yee
Affiliation: Penn State Hershey Cancer Institute, 500 University Drive, Hershey, Pennsylvania, 17033, United States of America.
Neuroendocrine tumor behaves variably from indolent to aggressive, and its incidence has been rising. While
surgical resection has been the mainstay treatment for localized tumors, the therapeutic options for advanced or metastatic
diseases have been very limited until recently. Octreotide has been conventionally used for control of symptoms in patients
with carcinoid syndrome as well as for their anti-tumor effects. Advances in understanding the molecular basis of
growth control and development of targeted agents have led to the approval of everolimus and sunitinib for treatment of
pancreatic neuroendocrine tumors. These small molecule drugs target the genetic pathways that mediate mitogen-induced
signaling involving mammalian target of rapamycin and receptor tyrosine kinases, leading to suppression of tumor
growth. Emerging therapies with combination of cytotoxic chemotherapy and targeted agents have begun to show promising
results. Continued efforts are necessary to understand the signaling mechanisms that underlie the initiation and progression
of neuroendocrine neoplasms. Further development of clinically useful biomarkers and therapeutic agents that
target multiple sites of the signaling complex is expected to generate drugs with tumor-specific actions and it may help
overcome resistance to chemotherapy. Ultimately, the goal is to develop effective and safe treatment tailored to the individual
patients by targeting the molecular phenotype of neuroendocrine tumors.
Keywords: Everolimus, genetic targets, neuroendocrine tumor, octreotide, sunitinib, targeted therapy.
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