Research in neuroendocrine tumours (NETs)

We are always learning more about cancer. Researchers and healthcare professionals use what they learn from research studies to develop better practices that will find and treat neuroendocrine tumours (NETs). They are also looking for ways to improve the quality of life of people with NETs.

The following is a selection of research showing promise for NETs. We’ve included information from PubMed, which is the research database of the National Library of Medicine. Each research article in PubMed has an identity number (called a PMID) that links to a brief overview (called an abstract). You can find information about ongoing clinical trials in Canada from or Clinical trials are given a national clinical trial (NCT) number. The NCT number links to information about the clinical trial.

Diagnosis and prognosis

A key area of research looks at better ways to diagnose and stage NETs. Researchers are also trying to find ways to help doctors predict a prognosis (the probability that the cancer can be successfully treated or that it will come back after treatment). The following is noteworthy research into diagnosis and prognosis.

Combined PET-CT scan using certain radiopharmaceuticals, such as 18F-FDOPA or 68Ga-DOTATATE, helps doctors diagnose, stage and plan treatments for NETs (Journal of Clinical Oncology, PMID 26712231; European Journal of Radiology, PMID 26152870; European Journal of Nuclear Medicine and Molecular Imaging, PMID 23417499). Find out more about positron emission tomography (PET) scan and computed tomography (CT) scan.

Biomarkers are substances, such as proteins, genes or pieces of genetic material like DNA and RNA, that are naturally in the body. They can be measured in body fluids like blood and urine or tissue that has been removed from the body. A gene mutation or a change in the normal amount of a biomarker can mean that a person has a certain type of cancer. If your doctor thinks you might have a neuroendocrine tumour (NET), biomarkers that look for these changes may help confirm the diagnosis. Biomarker tests can also help doctors predict the prognosis or response to treatment in people with NETs. Researchers are looking at the following biomarkers to see if they can help doctors diagnose, predict a prognosis for and find out which treatments will benefit a person with a NET (Cancers, PMID 27023611; European Journal of Nuclear Medicine and Molecular Imaging, PMID 26596723; Surgery, PMID 26456125; The Lancet Oncology, PMID 26370353; Clinical Cancer Research, PMID 26199388; The American Journal of Gastroenterology, PMID 26032155):

  • a copy of the DNA in a gene (called a gene transcript), which converts the instructions in DNA into proteins or other useful products that make cells work
  • short pieces of RNA (called microRNA)
  • cancer cells circulating in the blood (called circulating tumour cells)

Molecular profiling is a type of testing that looks at the genetic characteristics of tumours and finds unique biomarkers in the tumours. Researchers hope that molecular profiling will help doctors identify the best treatments for certain types of cancer, including NETs. Molecular profiling will also help doctors create targeted therapies for each cancer based on the specific genetic makeup of the tumour. A clinical trial in Canada is doing molecular profiling on tissue and blood samples from people with NETs that have been treated with targeted therapy (, NCT 02586844).


Researchers are looking for new ways to improve treatment for NETs. Advances in cancer treatment and new ways to manage the side effects from treatment have improved the outlook and quality of life for many people with cancer.

Targeted therapy

Targeted therapy uses drugs to target specific molecules (for example, proteins) on the surface of or inside cancer cells. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells. The following is noteworthy research into targeted therapy for NETs.

Everolimus(Afinitor) is a targeted therapy drug called an mTOR inhibitor. mTOR inhibitors work by blocking the action of a protein that controls cell growth and reproduction. Everolimus is showing promise as a treatment for gastrointestinal (GI) and lung NETs that continue to grow and spread (are progressive). A phase III trial found that people given everolimus lived longer without the cancer getting worse (called progression-free survival) than people who were given a placebo (The Lancet, PMID 26703889).

Bevacizumab(Avastin) is a type of vascular endothelial growth factor (VEGF) inhibitor. It stops cancer cells from forming new blood vessels, which they need to grow and develop. Researchers are looking at how effective and safe bevacizumab is in treating metastatic or progressive NETs that continue to grow and spread. They are also studying bevacizumab in combination with other drugs, such as chemotherapy or an mTOR inhibitor (Journal of Clinical Oncology, PMID 25488966; European Journal of Cancer, PMID 25454413, PMID 25454412; BMC Cancer, PMID 24628963).

Pasireotide (Signifor) is a somatostatin analogue drug. This type of drug is used to control symptoms of carcinoid syndrome and slow down the growth of metastatic NETs. Researchers are studying pasireotide as a treatment for NETs when the cancer doesn’t respond to other somatostatin analogues, such as octreotide (Sandostatin). A phase III clinical trial found that pasireotide long-acting release (LAR) controlled symptoms as well as octreotide LAR. It also found there was longer progression-free survival with pasireotide LAR than with octreotide LAR (Drug Design, Development and Therapy, PMID 26366058).

Peptide receptor radionuclide therapy (PRRT)

PRRT uses a radioactive material (called a radioisotope) combined with a somatostatin analogue drug that targets specific molecules on the surface of cancer cells. Cancer cells take up the radioactive material, which destroys them. Lutetium-177 octreotate (Lutathera) is a type of PRRT that has been approved by Health Canada to treat unresectable or metastatic, well-differentiated, somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours that continues to grow and spread (, NCT 02754297).

Supportive care

Living with cancer can be challenging in many different ways. Supportive care can help people cope with cancer, its treatment and possible side effects. The following is noteworthy research into supportive care for NETs.

Telotristat etiprate can help control diarrhea in people with carcinoid syndrome. Doctors usually give a somatostatin analogue, such as octreotide, to control symptoms of carcinoid syndrome. Researchers are studying telotristat etiprate as an alternative treatment when a somatostatin analogue doesn’t control diarrhea well enough (The Journal of Clinical Endocrinology and Metabolism, PMID 25636046; Endocrine-Related Cancer, PMID 25012985).

Heart valve surgery can treat heart damage from carcinoid syndrome (called carcinoid heart disease). This surgery helps control symptoms of heart damage and improve prognosis and survival (Journal of the American College of Cardiology, PMID 26564596; Interactive Cardiovascular and Thoracic Surgery, PMID 24812331).

Learn more about cancer research

Researchers continue to try to find out more about NETs. Clinical trials are research studies that test new ways to prevent, detect, treat or manage cancer. Clinical trials provide information about the safety and effectiveness of new approaches to see if they should become widely available. Most of the standard treatments for NETs were first shown to be effective through clinical trials.

Find out more about clinical trials.

Expert review and references

  • Albanus DR, Apitzsch J, Erdem Z, et al . Clinical value of 68Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). European Journal of Radiology. 2015.
  • Balogova S, Talbot JN, Nataf V, et al . 18F-fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type. European Journal of Nuclear Medicine and Molecular Imaging. 2013:
  • Berruti A, Fazio N, Ferrero A, et al . Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the XELBEVOCT study . BMC Cancer . 2014 .
  • Bodei L, Kidd M, Modlin IM, et al . Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors. European Journal of Nuclear Medicine and Molecular Imaging. 2016.
  • Canadian Partnership Against Cancer. Canadian Cancer Trials. Canadian Partnership Against Cancer;
  • Connolly HM, Schaff HV, Abel MD, et al . Early and late outcomes of surgical treatment in carcinoid heart disease. Journal of the American College of Cardiology. 2015.
  • Demes M, Aszyk C, Bartsch H, Schirren J, Fisseler-Eckhoff A . Differential miRNA-expression as an adjunctive diagnostic tool in neuroendocrine tumors of the lung . Cancers . 2016 .
  • Ducreux M, Dahan L, Smith D, et al . Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial): a phase II non-randomised trial. European Journal of Cancer. 2014.
  • Hobday TJ, Qin R, Reidy-Lagunes D, et al . Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. Journal of Clinical Oncology. 2015.
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  • Kulke MH, O'Dorisio T, Phan A, et al . Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide . Endocrine-Related Cancer . 2014 .
  • Manoly I, McAnelly SL, Sriskandarajah S, McLaughlin KE . Prognosis of patients with carcinoid heart disease after valvular surgery . Interactive Cardiovascular and Thoracic Surgery . 2014 .
  • Mitry E, Walter T, Baudin E, et al . Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial): a phase II non-randomised trial. European Journal of Cancer. 2014.
  • Modlin IM, Frilling A, Salem RR, et al . Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies. Surgery. 2016.
  • Modlin IM, Kidd M, Bodei L, Drozdov I, Aslanian H . The clinical utility of a novel blood-based multi-transcriptome assay for the diagnosis of neuroendocrine tumors of the gastrointestinal tract. American Journal of Gastroenterology. 2015.
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  • Pavel M, Horsch D, Caplin M, et al . Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial . Journal of Clinical Endocrinology and Metabolism . 2015 .
  • Sadowski SM, Neychev V, Millo C, et al . Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. Journal of Clinical Oncology. 2016.
  • Wolin EM, Jarzab B, Eriksson B, et al . Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. Drug Design, Development and Therapy. 2015:
  • Yao JC, Fazio N, Singh S, et al . Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016.