Everolimus and pancreatic neuroendocrine tumors (PNETs): Activity, resistance and how to overcome it

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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 languageEnglish
Pages (from-to)S89-S94
JournalInternational Journal of Surgery
Volume21
Issue numberS1
DOIs
Publication statusPublished - Sep 1 2015

Fingerprint

Neuroendocrine Tumors
Sirolimus
Drug Resistance
Neoplasms
Appendix
United States Food and Drug Administration
Renal Cell Carcinoma
Gastrointestinal Tract
Pancreas
Everolimus
Hormones
Breast Neoplasms
Pharmaceutical Preparations

Keywords

  • Chemokine
  • Drug resistance
  • Everolimus
  • M-TOR pathway
  • Pancreatic neuroendocrine tumor

ASJC Scopus subject areas

  • Surgery

Cite this

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title = "Everolimus and pancreatic neuroendocrine tumors (PNETs): Activity, resistance and how to overcome it",
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.",
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author = "Monica Capozzi and Ieran{\`o} Caterina and {De Divitiis}, Chiara and {von Arx}, Claudia and Piera Maiolino and Fabiana Tatangelo and Ernesta Cavalcanti and {Di Girolamo}, Elena and Iaffaioli, {Rosario Vincenzo} and Stefania Scala and Salvatore Tafuto",
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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

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