Abstract
Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms. Currently Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is the most promising drug for patients with unresectable, metastatic disease, in progressive well-differentiated PNETs and many studies are ongoing to demonstrate its effects on the other neuroendocrine histotipes. Food and Drug Administration (FDA) and European Medicines Agency (EMA) registered Everolimus in advanced/metastatic breast cancer, in advanced/metastatic renal cell carcinoma and in well/moderately differentiated pancreatic neuroendocrine tumors. Nevertheless only a subset of patients respond to the therapy due to the development of drug resistance. Thus the powerful Everolimus antitumor activity have prompted extensive efforts to overcome drug resistance and to maximize clinical benefit. In this review we aim to summarize current knowledge on mechanisms of Everolimus and other mTOR inhibitors molecules resistance with the intent to overcome it.
| Original language | English |
|---|---|
| Pages (from-to) | S89-S94 |
| Journal | International Journal of Surgery |
| Volume | 21 |
| Issue number | S1 |
| DOIs | |
| Publication status | Published - Sep 1 2015 |
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Keywords
- Chemokine
- Drug resistance
- Everolimus
- M-TOR pathway
- Pancreatic neuroendocrine tumor
ASJC Scopus subject areas
- Surgery
Cite this
Everolimus and pancreatic neuroendocrine tumors (PNETs) : Activity, resistance and how to overcome it. / Capozzi, Monica; Caterina, Ieranò; De Divitiis, Chiara; von Arx, Claudia; Maiolino, Piera; Tatangelo, Fabiana; Cavalcanti, Ernesta; Di Girolamo, Elena; Iaffaioli, Rosario Vincenzo; Scala, Stefania; Tafuto, Salvatore.
In: International Journal of Surgery, Vol. 21, No. S1, 01.09.2015, p. S89-S94.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Everolimus and pancreatic neuroendocrine tumors (PNETs)
T2 - Activity, resistance and how to overcome it
AU - Capozzi, Monica
AU - Caterina, Ieranò
AU - De Divitiis, Chiara
AU - von Arx, Claudia
AU - Maiolino, Piera
AU - Tatangelo, Fabiana
AU - Cavalcanti, Ernesta
AU - Di Girolamo, Elena
AU - Iaffaioli, Rosario Vincenzo
AU - Scala, Stefania
AU - Tafuto, Salvatore
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms. Currently Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is the most promising drug for patients with unresectable, metastatic disease, in progressive well-differentiated PNETs and many studies are ongoing to demonstrate its effects on the other neuroendocrine histotipes. Food and Drug Administration (FDA) and European Medicines Agency (EMA) registered Everolimus in advanced/metastatic breast cancer, in advanced/metastatic renal cell carcinoma and in well/moderately differentiated pancreatic neuroendocrine tumors. Nevertheless only a subset of patients respond to the therapy due to the development of drug resistance. Thus the powerful Everolimus antitumor activity have prompted extensive efforts to overcome drug resistance and to maximize clinical benefit. In this review we aim to summarize current knowledge on mechanisms of Everolimus and other mTOR inhibitors molecules resistance with the intent to overcome it.
AB - Neuroendocrine tumors (NET) are rare malignancies, with the most common site of origin being from the gastrointestinal tract, particularly the pancreas, small bowel and appendix. Pancreatic neuroendocrine tumors (PNETs) can be functional, hormone secreting tumors, and can have distinctive symptoms leading to the diagnosis. In contrast nonfunctional tumors, the majority of PNETs, usually present later either incidentally or due to tumor bulk symptoms. Currently Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is the most promising drug for patients with unresectable, metastatic disease, in progressive well-differentiated PNETs and many studies are ongoing to demonstrate its effects on the other neuroendocrine histotipes. Food and Drug Administration (FDA) and European Medicines Agency (EMA) registered Everolimus in advanced/metastatic breast cancer, in advanced/metastatic renal cell carcinoma and in well/moderately differentiated pancreatic neuroendocrine tumors. Nevertheless only a subset of patients respond to the therapy due to the development of drug resistance. Thus the powerful Everolimus antitumor activity have prompted extensive efforts to overcome drug resistance and to maximize clinical benefit. In this review we aim to summarize current knowledge on mechanisms of Everolimus and other mTOR inhibitors molecules resistance with the intent to overcome it.
KW - Chemokine
KW - Drug resistance
KW - Everolimus
KW - M-TOR pathway
KW - Pancreatic neuroendocrine tumor
UR - http://www.scopus.com/inward/record.url?scp=84940447992&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84940447992&partnerID=8YFLogxK
U2 - 10.1016/j.ijsu.2015.06.064
DO - 10.1016/j.ijsu.2015.06.064
M3 - Article
C2 - 26123382
AN - SCOPUS:84940447992
VL - 21
SP - S89-S94
JO - International Journal of Surgery
JF - International Journal of Surgery
SN - 1743-9191
IS - S1
ER -