TY - JOUR
T1 - Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms
AU - NIKE Group
AU - Grillo, Federica
AU - Florio, Tullio
AU - Ferraù, Francesco
AU - Kara, Elda
AU - Fanciulli, Giuseppe
AU - Faggiano, Antongiulio
AU - Colao, Annamaria
PY - 2018/9/1
Y1 - 2018/9/1
N2 - In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multitarget tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by Regulatory Agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in-depth review on the studies published on the MTKIs in neuroendocrine tumors such as axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on the Clinical Trial Registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastroenteropancreatic and lung NENs identifies in vitro and in vivo studies, which demonstrate anti-tumor activity of diverse MTKIs on neuroendocrine cells and tumors. Moreover, for the first time in the literature, we report an updated view concerning the upcoming clinical trials in this field: presently, phase I, II and III clinical trials are ongoing and will include, overall, a staggering 1667 patients. This fervid activity underlines the increasing interest of the scientific community in the use of emerging MTKIs in NEN treatment.
AB - In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multitarget tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by Regulatory Agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in-depth review on the studies published on the MTKIs in neuroendocrine tumors such as axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on the Clinical Trial Registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastroenteropancreatic and lung NENs identifies in vitro and in vivo studies, which demonstrate anti-tumor activity of diverse MTKIs on neuroendocrine cells and tumors. Moreover, for the first time in the literature, we report an updated view concerning the upcoming clinical trials in this field: presently, phase I, II and III clinical trials are ongoing and will include, overall, a staggering 1667 patients. This fervid activity underlines the increasing interest of the scientific community in the use of emerging MTKIs in NEN treatment.
KW - Neuroendocrine tumors
KW - Tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85051227617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051227617&partnerID=8YFLogxK
U2 - 10.1530/ERC-17-0531
DO - 10.1530/ERC-17-0531
M3 - Review article
AN - SCOPUS:85051227617
VL - 25
SP - R453-R466
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
SN - 1351-0088
IS - 9
ER -