Neuroendocrine Cancer is the 10th most prevalent cancer in England and the second most prevalent cancer of the Gastrointestinal tract.
Lives could be saved if we diagnosed people earlier, developed new and more effective treatments and ensure people, irrespective of where they live, see the right person at the right time and in the right place.
There have been major advances in understanding and treating people affected by Neuroendocrine Cancer in the past 30 years and these advances have all come through research.
In this section you will find information about:
As part of the Neuroendocrine Cancer UK Virtual Summit 2020, NCUK Cancer Support Co-ordinator, Kate Quirk talks about understanding research & reports back from the International Neuroendocrine Cancer Alliance, INCA. Select play to watch.
Patient involvement in clinical trials and research is crucial for breakthroughs in the Neuroendocrine Cancer community. By actively participating in trial design, patients can influence research priorities, contribute practical insights, and advocate for their needs, ultimately driving advancements and ensuring their inclusion in the process. Select play to watch. Select here to learn more about this video.
Clinical trials are used to find out if new treatments and techniques are safer and more effective than the ones that already exist or discovering if existing treatments can be used in different ways. Without trials we really cannot make progress.
You may be offered the choice to take part in a clinical trial as part of your treatment. Before you decide if a clinical trial is right for you think about the pros and cons, ask questions and find out what it involves.
In this guide we cover topics such as;
- How Clinical Trials are Run
- Join a Clinical Trial
- Finding a Clinical Trial
- How to use Clinical Trials databases
- Clinical trials FAQs.
Gathering data is vital, and we get involved in a number of research projects both Nationally and Internationally, ensuring that the patient perspective is heard. Below you will see a snapshot of some of our work. Thank you to each and every one of you who completes a questionnaire or responds to a survey. It is SO important to be able to share your views – to bring your voice to a platform where it can be listened to and acted on. If you think you can help or you are willing to take part in any of our research projects then do let us know.
Select the image to learn more.
Incidence and survival of neuroendocrine neoplasia in England 1995–2018: A retrospective, population-based study.
Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients, patient advocates and NET health care professionals.
Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013–2015.
Presenting Symptoms and Delay in Diagnosis of Gastrointestinal and Pancreatic Neuroendocrine Tumours.
Who can take part in research?
Everyone can make a difference, whatever their circumstances. Research involves people of all ages and backgrounds, to help improve health and care for all.
Types of research you could get involved in
There are many different types of research. For example, some studies test new treatments or require samples. Others may involve interviews or surveys.
This short video by the National Institute for Health Research will tell you more.
Select the image to learn more.
No surveys at present
Advancing Research support
Learn more about how you can get involved in our ‘Advancing Research’ campaign.
The purpose of biobanking is to improve the prevention, diagnosis and treatment of a wide range of illnesses – including rare or uncommon cancers like Neuroendocrine Cancer.
Biobanking is the process of collecting and storing removed tissue (for example following an operation or biopsy procedure) no longer needed for diagnosis or treatment and / or taking a blood sample – for use in current or future research.
Organ and Body Donation
We are occasionally asked whether it is still possible to donate your body to science – and yes you can.
The same organisation that regulates body donation also regulates and supplies advice and information on organ and tissue donation.
Neuroendocrine Cancer UK’s Research Grants
Complex and groundbreaking pilot research projects made possible through your support. Getting research into Neuroendocrine Cancer off the ground can be challenging, and our ‘prime pumping’ grants can lead to much larger international grants. Three of our research grants so far have done just this.
Our research grants are funded through our dedicated Clinical Fund. Our grants are open to all healthcare professionals in the UK with no geographical restrictions. Our peer review process is dependent on the size and complexity of the study: for clinical pilot studies we have a dedicated peer review group made up of specialist NET physicians, researchers, a nurse and a patient. All reviewers are external to the investigators host institution. The group members will be pulled together based on the applications received. It is not a static membership. For our quality of life and psychosocial research we have a group comprised of psychotherapists, a nurse, a medic, 2 patients and 2 carers. Our epidemiology work is run through a steering committee including staff from Neuroendocrine Cancer UK.
Neuroendocrine Cancer UK is a National Institute for Health Research (NIHR) non-commercial Partner. This means the studies that we fund may be eligible to access the NIHR Study Support Service which is provided by the NIHR Clinical Research Network. The NIHR Clinical Research Network can now support health and social care research taking place in non-NHS settings, such as studies running in care homes or hospices, or public health research taking place in schools and other community settings. Read the full policy: Eligibility Criteria for NIHR Clinical Research Network Support.
In partnership with your local R&D office, we encourage you to involve your local NIHR Clinical Research Network team in discussions as early as possible when planning your study. This will enable you to fully benefit from the support available through the NIHR Study Support Service. To find out more, please visit: www.nihr.ac.uk/study-support-service
If your study involves NHS sites in England you will need to apply for Health Research Authority Approval. For guidance on submitting an application please visit: www.hra.nhs.uk.
- 2022 Recipient
- 2021 Recipient
- 2020 Recipient
- 2019 Recipients
- 2018 Recipients
- 2016 Recipient
- 2015 Recipient
- 2014 Recipients
Dr Garan Jones – Research Grant Winner
We are delighted to award the 2021 NCUK grant to Dr Melissa Frizziero, The Christie Hospital, Manchester.
‘Epigenetic-based biomarker discovery for Extra-Pulmonary Neuroendocrine Carcinoma’ (EP-NEC).
NCUK-UKINETS Grant Award 2021
Epigenetic-based biomarker discovery for Extra-Pulmonary NeuroEndocrine Carcinoma (EP-NEC)
Lay summary of the project:
NeuroEndocrine Carcinomas (NECs) are rare but aggressive, rapidly growing cancers that can originate from any organ in the body. Patients with NEC are becoming more commonly encountered in clinic. The majority of patients with NEC present with distant metastases at diagnosis meaning that they’re not amenable to curative treatment; these patients have a short life expectancy (<12 months, on average), and can only be offered chemotherapy with palliative intent or best supportive care (symptom control only). While significant research effort has been invested into NECs originating from the lung, which are the most common, NECs from outside of the lung, so-called Extra-Pulmonary (EP)-NECs, remain poorly studied. Tumour material shed into the patient bloodstream, such as tumour-derived DNA (so called ‘circulating tumour DNA’ or ctDNA) or entire tumour cells (so called ‘circulating tumour cells’ or CTCs), can provide useful information for the management of these patients. This material can be obtained through a simple blood draw and the procedure is known as ‘liquid biopsy’. Recent studies have shown that methods looking at epigenetic changes in the ctDNA (epigenetic-based ctDNA analysis) have increased ability to detect ctDNA in a variety of cancer types as compared to conventional methods looking at genetic changes in the ctDNA.
The Cancer Research UK Manchester Institute Cancer Biomarker Centre (CRUK MI CBC) is a laboratory with worldwide expertise in liquid biopsies and NEC research. Under the framework of a collaboration between CRUK MI CBC and The Manchester European Neuroendocrine Tumour Society Centre of Excellence at The Christie NHS Foundation Trust, a study has been setup to investigate whether liquid biopsies can aid in the clinical management of patients with EP-NEC. As part of this study, we have been collecting serial blood samples for ctDNA analysis from patients with an EP-NEC diagnosis undergoing palliative chemotherapy at The Christie NHS Foundation Trust in Manchester. The aim of this project is to assess whether a novel method for epigenetic-based ctDNA analysis is feasible in patients with EP-NEC and can help improve the management and treatment outcomes of these patients.
We are delighted to award the 2020 NCUK grant to Dr Marc Ooft, Consultant Histopathologist, Kings College Hospital.
His research alongside the NET GeCIP group is focusing on ‘Improving patient stratification through epigenetic and tumour microenvironmnet analysis of the 100,000 Genomes project neuroendocrine tumour cohort.’
We would also like to thank Mr P Moxham for his generous donation towards our research grant.
Prof Mark Pritchard, Professor of Gastroenterology, Institute of Translational Medicine,
University of Liverpool and Head of Liverpool ENETS Centre of Excellence at Liverpool University Hospitals NHS Foundation Trust
The aim of this project is to develop and characterise primary cultures from the tumours as well as the adjacent unaffected mucosa of patients with low grade type 1 and type 3 gastric NETs. These gastroids will then be cryopreserved in order to provide tools that can be used for future investigations about the pathogenesis and treatment of gastric NETs. We believe that we have the unique combination of a large cohort of patients with gastric NETs and the required laboratory expertise to successfully complete this project.
2019 Recipient update (2021)
Understanding how type I gastric neuroendocrine tumours develop
Prof Mark Pritchard, University of Liverpool
There are three main types of neuroendocrine tumour (NET) that develop in the stomach. The commonest type (type 1) develops in patients who have an autoimmune condition that results in destruction of the acid producing (parietal) cells in the stomach. Many type 1 gastric NET patients also have pernicious anaemia and require regular vitamin B12 injections. As a result of their stomachs producing little or no acid, these patients have very high levels of a hormone called gastrin in their bloodstream and it is this hormone that is believed to be responsible for the development of type 1 gastric NETs.
The long term outlook for most patients who have type 1 gastric NETs is very good. The majority of patients have small tumours and don’t actually need any type of active treatment. However a minority of patients have larger tumours and these may need to be removed either via an endoscope or by surgery. In 2010-4 we conducted a clinical trial involving eight patients in Liverpool and eight in Norway to test a potential new tablet treatment for type I gastric NETs (funded by Trio Medicines Ltd). If successful, this might mean that in future some type I gastric NET patients might be able to avoid surgery. The new drug (Netazepide) blocks the effects of gastrin. The trial showed promising results with a shrinkage in the size and number of the tumours in many patients and the treatment also resulted in no serious side effects 1,2. Trio medicines Ltd are still working on the development of this drug, so at the moment it is not available for general prescription.
In 2014, we were awarded a research grant by Neuroendocrine Cancer UK to investigate how Netazepide was exerting its effects in these patients. We used stomach biopsy samples that had been taken before, during and after the patients on this trial were being treated with Netazepide. We found that only 12 genes showed significantly decreased expression when the patients were taking Netazepide. One of these genes called pappalysin or PAPP-A2 was particularly interesting. This gene encodes a protein which is an enzyme that regulates how much of a growth factor called insulin-like growth factor is present in the stomach. We performed several additional experiments which demonstrated that this signalling pathway appears to both be important during gastric NET development and in determining how these tumours respond to Netazepide treatment. As well as increasing our scientific understanding about type I gastric NETs, our research has at least partially explained how Netazepide works and it also provides opportunities to design other potential new drug treatments for type I gastric NETs in the future.
The results of our study were published in the scientific journal ‘Cellular and Molecular Gastroenterology and Hepatology’ in 2020 and are available online to read by anyone who is interested 3.
In 2019 we were awarded another grant by Neuroendocrine Cancer UK to try to grow gastric NET cells in the laboratory in order to be able to test the effects of potential new treatments before actually giving these drugs to patients within a clinical trial. This research is still ongoing and we hope to provide an update about our findings in due course.
1. Moore AR, Boyce M, Steele IA, Campbell F, Varro A, Pritchard DM. Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised trial of patients with chronic atrophic gastritis. PLoS One. 2013;8(10):e76462.
2. Boyce M, Moore AR, Sagatun L, et al. Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis. Br J Clin Pharmacol. 2017;83(3):466-475.
3. Lloyd KA, Parsons BN, Burkitt MD, et al. Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors. Cell Mol Gastroenterol Hepatol. 2020;10(1):113-132.
The TRACERx – (TRAcking Cancer Evolution through therapy (Rx))
One of the winners of the UKINETs/NPF grants was one of the TRACERx team. We are delighted that Lung NETs will now be included in this research project. Want to know more about TRACERx? Read below….
The TRACERx (TRAcking Cancer Evolution through therapy (Rx)) lung study is a multi-million-pound research project taking place over nine years, which will transform our understanding of non-small cell lung cancer (NSCLC) and take a practical step towards an era of precision medicine. The study will uncover mechanisms of cancer evolution by analysing the intratumour heterogeneity in lung tumours from approximately 850 patients and tracking its evolutionary trajectory from diagnosis through to relapse. At £14 million, it’s the biggest single investment in lung cancer research by Cancer Research UK, and the start of a strategic UK-wide focus on the disease, aimed at making real progress for patients.
Led by Professor Charles Swanton at UCL, the study will bring together a network of experts from different disciplines to help integrate clinical and genomic data and identify patients who could benefit from trials of new, targeted treatments. In addition, it will use a whole suite of cutting edge analytical techniques on these patients’ tumour samples, giving unprecedented insight into the genomic landscape of primary and metastatic tumours and the impact of treatment upon this landscape.
In future, TRACERx will enable us to define how intratumour heterogeneity impacts upon cancer immunity throughout tumour evolution and therapy. Such studies will help define how the clinical evaluation of intratumour heterogeneity can inform patient stratification and the development of combinatorial therapies incorporating conventional, targeted and immune-based therapeutics.
Intratumour heterogeneity is increasingly recognised as a major hurdle to achieve improvements in therapeutic outcome and biomarker validation. Intratumour genetic diversity provides a substrate for tumour adaptation and evolution. However, the evolutionary genomic landscape of non-small cell lung cancer (NSCLC) and how it changes through the disease course has not been studied in detail.
The other worthy winner was Kate Lines, a PostDoctoral researcher, who works at the Radcliffe Department of Medicine in Oxford, alongside Professor Raj Thakker. She is continuing here work on molecular genetics in pancreatic neuroendocrine tumours.
“I am delighted and very grateful to have been awarded NET patient foundation award at this years UKINETs meeting. I am very much looking forward to beginning the study. As an early career scientist, this grant is especially important as the data generated from the project will help form the basis of my future NET research career”.
The aim of the project is to develop a new drug for the treatment of pancreatic neuroendocrine tumours (PNETs). We have previously shown that a drug called JQ1, which inhibits the function of a family of proteins called the BET family, could reduce the number of PNET cells in the laboratory. This family of proteins help to control the expression of genes that promote tumour cell growth and prevent tumour cell death, by binding to chemical marks in specific DNA regions, also known as epigenetic regulation. Therefore, by inhibiting the activity of the BET proteins we were able to prevent the cell growth and increase cell death.
Although JQ1 has shown promising results in PNETs, similar to a chemotherapy, it can act on any cell that expresses the BET proteins, and therefore may have side effects. The focus of this study is therefore to generate a new drug that specifically targets JQ1 only to NET cells or tissues. To do this we are using a man made version of the hormone somatostatin, called a somatostatin analogue. Receptors that somatostatin binds to are only expressed in certain endocrine tissues, and are seen in high levels in PNETs. Therefore by making a drug with a somatostatin analogue joined to JQ1, we plan to target JQ1 only to the PNET cells. We will test the ability of this new somatostatin-JQ1 drug to reduce the number of PNET cells. If successful, the ultimate aim is to use this data to plan a clinical trial of the somatostatin-JQ1 drug in PNET patients.”
2018 Recipient update (2021)
Project: Evaluation of somatostatin analogue-JQ1 conjugates for the treatment of pancreatic neuroendocrine tumours.
Pancreatic neuroendocrine tumours (PNETs) are increasing in incidence, and have a 5-year survival rate of <50%. This is largely because, despite recent advances, current treatments are often ineffective, and therefore additional therapeutic agents are required. Epigenetic inhibitors may offer a novel class of anti-cancer drugs, as PNETs harbour mutations of chromatin remodelling genes including ATRX and DAXX, while menin, encoded by MEN1, interacts with chromatin remodelling proteins, including the histone methyltransferase MLL1. Furthermore, we have previously demonstrated that JQ1, a bromo and extra terminal domain inhibitor (BETi) that prevents binding of the BET family of proteins to acetylated histone residues, significantly decreased proliferation and increased apoptosis of a human PNET cell line (BON-1), and PNETs in a pancreatic cell specific Men1 knockout mouse model. However, JQ1 is effective against multiple tumours, indicating it may lack specificity. This may lead to significant off-target adverse effects, which could be overcome by targeting JQ1 specifically to PNET cells. Neuroendocrine tissues, including PNETs express somatostatin receptors (SSTRs), of which there are 5, SSTR1-5, that play a role in hormone synthesis and secretion. Analogues that bind these receptors, including the SSTR2-binding somatostatin analogue octreotide, have also been shown to control symptoms in NET patients.
In our study, we have designed and synthesised a novel molecule that is a conjugate of an orally active derivative of JQ1, OTX-015, that is currently undergoing clinical trials for leukaemia and glioblastoma, to the clinically used somatostatin analogue octreotide, via a protease degradable linker. We have undertaken dose escalation studies in conditional Men1 knockout mice that develop PNETs from 6 months of age, and in which we have confirmed the expression of SSTR 1, 2, 3 and 5 in the PNETs. These studies showed that the conjugate molecule is well tolerated in concentrations up to 50mg/kg, injected intraperitoneally, which is comparable to the concentration of JQ1 used in previous in vivo mouse studies. In addition, we have undertaken preliminary efficacy studies which indicate that the novel conjugate drug can reduce proliferation of the PNETs, compared to control (vehicle only) mice. We are now in the process of applying for additional funding to undertake further in vivo studies to validate these preliminary studies and to confirm if the drug is safe and efficacious. Thus, we have developed a novel NET-targeted BETi that is now available for detailed preclinical in vitro and in vivo evaluation.
Congratulations to Christodoulos Pipinikas, the recipient of our 2016 award, which will be funding this exciting project:
Using an integrated approach combining data generated through the use of different, advanced molecular tools, we have previously demonstrated that neuroendocrine tumours of the pancreas and gastrointestinal tract are highly epigenetically dysregulated and have identified several altered biological pathways and genes that may form the basis for the development of novel therapeutic targets. In addition, our group has identified specific molecular disease subtypes associated with a significant impact on patients’ survival, indicating that these may benefit from different treatments. Using a similar approach, we would like to extend our understanding of the key molecular events involved in the development and progression of bronchopulmonary neuroendocrine tumours (BP-NETs). BP-NETs represent a significant disease burden with socioeconomic extensions due to their increased incidence and decreased 5-year survival rates. BP-NETs comprise approximately 20-25% of all lung cancers and represent a spectrum of tumours arising from neuroendocrine cells of the bronchopulmonary epithelium. Tumour classification into the correct histological sub-group is strongly predictive of patients’ prognosis but relies on few, difficult to reproduce pathological parameters which are often affected by a high inter-observer variability. Therefore, the aim of this project is to identify novel and accurate molecular tools in order to improve the classification of these tumours. This, in turn, will provide better prognostic information and help with choosing more appropriate treatments. In addition, we aim to study the underlying pathogenic mechanisms involved in disease development and progression through the use of large-scale integrated omics analyses.
Jorge Barriuso who works with Prof. Juan Valle at the Christie Hospital was awarded £30,000. The aim of the project is to identify predictive genetic markers of exceptional response to targeted therapies, therefore allowing treatment stratification. Samples from the Christie NET biobank would be used for this pilot study.
This year the £30,000 grant will be funded solely by the NET Patient Foundation, the details and timeline for applying will be posted on the UKINETs and NET Patient Foundation websites in July 2016. The successful applicant will be invited to present their project and results at the UKINETs annual meeting.
Dr Davlinder Mandair is a trainee gastroenterologist who is currently undertaking a PhD under the supervision of Prof Tim Meyer, Prof Martin Caplin and Dr Chrissie Thirlwell at the UCL Cancer Institute in London.
The project builds on previous work conducted in Prof Meyer’s Lab which demonstrated, for the first time, that circulating tumour cells (CTCs) were detectable in the blood of patients with a range of NETs, and that their presence indicated an adverse prognosis. Technology has now advanced to the extent that detailed molecular characterisation can be conducted on single cells and this project will compare the genetic changes seen in primary tumour tissue with that of CTCs and also with cfDNA (pieces of DNA that arise from the tumour and can be found circulating in the blood stream).
If we can show that CTCs and cfDNA does indeed accurately represent the tumour, then we will be able to track how the tumour evolves over time and during treatment. This may allow clinicians treating patients with NETs to select the appropriate therapy and to anticipate the emergence of resistance. As cancer therapy becomes increasingly personalised, it is important that we can undertake this type of analysis so that patients can benefit fully from the new drugs that target specific cancer pathways.
Prof Ramage is a Consultant Physician in Gastroenterology and Hepatology, and lead clinician for the Neuroendocrine Tumour Service at King’s College Hospital NHS Foundation Trust.
The project will study the NETs that were identified in the Colorectal NET and the Bowel Cancer Screening Programme (BCSP). The aim is to understand how these were identified, how they were investigated and how they were treated.
The Bowel Cancer screening programme has screened 1 million people using faecal occult blood (FOB -blood in the stool) testing and 17,500 colonoscopies have been performed. Overall, 7.8% (women) and 11.6% (men) of the colonoscopies detected a colorectal (CR) cancer. However, the data regarding the NET tumours that were identified has not been analysed.
The incidence of CR NET in the general population is thought to be 1.3 per 100,000. The incidence in patients with positive FOB is unknown but CR cancer incidence is 46 per 100,000 in England and thus NET incidence might be 46/1.3 times less likely to be found than CR cancer. This would be 35.4 times less likely which would equate to 1772/ 35.4= 50 cases. It is also possible that some ileal carcinoids will have been found during colonoscopy, and these are twice as common as CR NET.
This study will identify how many CR and ileal NET were found by screening if screening has any value for earlier diagnosis. It will also establish how many of these were seen by NET specialists.
Support Our Research
We want and need more research for Neuroendocrine Cancer. No major research organisation has a dedicated research programme for this cancer type, therefore a vital part of our work is supporting researchers and specialist centres undertaking neuroendocrine research and encouraging more research to be carried out in the future.
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