Neuroendocrine
neoplasms (NEN) are a heterogeneous group of
tumors, whose incidence and prevalence are increasing. The clinical behavior of NEN is variable, ranging from well-differentiated slow growing
tumors to highly aggressive poorly differentiated
neuroendocrine carcinomas. The term
carcinoid is commonly used for the more benign variants of these
neoplasms. Most frequently,
carcinoids have their origin in the small intestine, followed by in the lung and other sites. Some of these
tumors are associated with the
carcinoid syndrome. The use of
somatostatin analogs has revolutionized the clinical management of patients with
carcinoids. However, although symptomatic relief and stabilization of
tumor growth for various periods of time are observed in many patients treated with
somatostatin analogs,
tumor regression is rare. Currently, there is no other powerful antiproliferative agent available for
carcinoids.
Mammalian target of rapamycin (mTOR), a main
protein kinase in the
phosphoinositide 3-kinase/Akt/
p70S6K signaling pathway, is an important intracellular mediator involved in multiple cellular functions including proliferation, differentiation, apoptosis,
tumorigenesis, and angiogenesis. Alterations of the normal activity of mTOR and of mTOR-related
kinases in this pathway have been found in a diversity of human
tumors, including NEN; therefore, mTOR pathway represents an attractive target for new anticancer
therapies. While
mTOR inhibitors, such as
everolimus, are established
therapy in pancreatic NEN, results from recent clinical trials indicate that
mTOR inhibitors may be also of value in the management of
carcinoids. However, further clinical trials will have to confirm efficacy and elucidate, in which subtypes and in which setting, these drugs might be most usefully applied.