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The pivotal role of mammalian target of rapamycin inhibition in the treatment of patients with neuroendocrine tumors.

ABSTRACT: Significant advances have been made toward understanding the biology of neuroendocrine tumors (NET) in terms of defining prognosis and improving clinical management; however, many unmet needs remain. The treatment landscape for NET has evolved, with the approval of the targeted agents everolimus and sunitinib for the treatment of advanced pancreatic NET in 2011 followed by the approval of everolimus for the treatment of advanced nonfunctional gastrointestinal and lung NET in 2016. Mammalian target of rapamycin (mTOR) and components of the mTOR pathway play pivotal roles in NET pathogenesis. Effects of the mTOR inhibitor everolimus have been well documented in preclinical and clinical studies, both as monotherapy and combination therapy. mTOR inhibition as backbone therapy within the NET treatment landscape is a focus of continuing research, which includes evaluation of the growing armamentarium of approved and investigational agents as potential combination partners. Data evaluating the clinical benefits of agents targeting mTOR and related pathways (alone and in combination) in the treatment of patients with NET continue to increase. Many of the findings to date are encouraging.

SUBMITTER: Phan AT

PROVIDER: S-EPMC5083749 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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The pivotal role of mammalian target of rapamycin inhibition in the treatment of patients with neuroendocrine tumors.

Phan Alexandria T AT Dave Bhuvanesh B

Cancer medicine 20160818 10

Significant advances have been made toward understanding the biology of neuroendocrine tumors (NET) in terms of defining prognosis and improving clinical management; however, many unmet needs remain. The treatment landscape for NET has evolved, with the approval of the targeted agents everolimus and sunitinib for the treatment of advanced pancreatic NET in 2011 followed by the approval of everolimus for the treatment of advanced nonfunctional gastrointestinal and lung NET in 2016. Mammalian targ ...[more]

PMID: 27539383

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Project description:: The carcinoid syndrome represents a set of signs and symptoms associated with neuroendocrine tumors (NETs) that occur primarily when metastases are developed in the liver, resulting in the worsening of quality of life. Serotonin plays a central role in the physiology of carcinoid syndrome by promoting intestinal motility. Somatostatin analogs (SSAs) have widely demonstrated their efficacy as symptomatic relievers of carcinoid syndrome, but this control is ephemeral, being reduced by approximately 50% within the first year. The exact mechanisms of resistance to SSAs are not fully understood, but it is believed that serotonin might be involved. Patients with carcinoid syndrome present with a significant increase in serotonin plasma levels and, consequently, in the soluble urinary metabolite 5-hydroxyindole acetic acid. Telotristat etiprate is a potent inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the synthesis of serotonin, that has demonstrated in the phase III TELESTAR clinical trial a significant improvement in the control of bowel movements in patients with NETs who have carcinoid syndrome and who have progressed to an SSA. Based on these results, telotristat etiprate has emerged as a potential new option in the treatment algorithm of symptomatic control of functioning NETs. However, some issues need to be clarified, such as the safety profile of the drug outside clinical trials, the benefit in quality of life, and the possible impact on tumor growth, as well as its role within sequencing or combination treatment strategies with pre-existing drugs effective in NET treatment.This article reviews the literature about carcinoid syndrome, which affects patients diagnosed with neuroendocrine tumors. Few articles have been published about this syndrome and its pathophysiology. Somatostatin analogs provide symptomatic relief; however, patients may become refractory to this strategy, usually within the first year of treatment. In this context, as an agent with an innovative mechanism of action, telotristat etiprate has demonstrated activity in a phase III trial, and findings may offer a path to an improve quality of life and prolonged survival for certain patients.

Dataset Information

The pivotal role of mammalian target of rapamycin inhibition in the treatment of patients with neuroendocrine tumors.

Publications

The pivotal role of mammalian target of rapamycin inhibition in the treatment of patients with neuroendocrine tumors.

Similar Datasets

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