You might not have heard of neuroendocrine tumours, or NETs, but chances are you know the name of someone who has had one.
It's the type of cancer Apple founder Steve Jobs and soul singer Aretha Franklin had. Despite these high-profile cases, this rare and deadly form of cancer has stayed largely under the public's radar.
What are neuroendocrine tumours?
Jobs and Franklin both had NETs starting in the pancreas, but the tumours can occur all over the body, specifically in any cells that make hormones.
For some people, these cancerous cells become out-of-control hormone factories resulting in a wide variety of problems including severe diarrhoea, hot flushes, fatigue, and, in rarer cases, stomach ulcers and low blood sugars.
In others, they grow silently, and only cause symptoms like pain when they have become large or have spread (metastasised).
Because NETs behave in many ways, they can be difficult for doctors to identify. In fact, worldwide 50 per cent of all NET patients suffer for up to nine years after their first symptom before finally getting a diagnosis.
This delay means in more than 50 per cent of cases, people have incurable, widespread 'Stage 4' or metastatic disease by the time they are diagnosed, leaving them with severe symptoms, low quality of life, few treatment options, and, in aggressive cases, only seven to 15 months to live.
Some types of NETs are caused by gene changes, or mutations, that run in families.
For example, the most heritable human cancer, pheochromocytoma, is a NET that is caused by familial mutations 40 per cent of the time. This means that diagnosing someone with a NET and knowing the genes that cause the cancer might not just be important for patients but for their families as well.
Now, a new partnership between both our teams - the University of Melbourne's Rare Disease Oncogenomics (RADIO) laboratory and the Peter MacCallum Cancer Centre's NET Unit (the first European NeuroEndocrine Tumour Society certified Centre of Excellence in the Southern Hemisphere) - will help bridge the gap between the clinic and the lab, developing better diagnostic tests and future treatment options for people with NETs.
Collaboration is key
Patients with NETs have many 'Why' questions: Why did I get this cancer? Why has my cancer spread? Why has my cancer grown during treatment? What is the best treatment for my disease?
Many of these questions still need answering because clinical research, like trials of new treatments, and laboratory research into the biology of NETs are largely underfunded and siloed from each other in Australia.
This is a missed opportunity for doctors and scientists to work together to understand crucial elements of the disease, like the biological reasons for why or why not a patient responds to a new treatment.
Coming to the clinic
Like many forms of rare cancer, NETs are still poorly understood, and treating them effectively is a complex task.
This is why when patients are referred to the Peter Mac NET Unit, often from a GP or their local specialist, they are introduced to a highly skilled, multi-disciplinary team of experts.
Patients meet a range of specialists: oncologists for treatments to stop the NET from growing; nuclear medicine specialists for scans to determine how widespread the tumour is and whether it can be treated with intravenous radiation therapy (peptide receptor radionuclide therapy); endocrinologists to help manage the symptoms of excessive hormones; surgeons if needed to take out a NET or help deal with bowel or bile duct blockages; pathologists to diagnose NETs; Familial Cancer specialists to support patients and families with inherited NET cancer syndromes; and dieticians to help maintain good nutrition.
Specialist nurses help coordinate patient care and support patients over the phone. Doctor and GPs across Australia and New Zealand can also get advice from the NET Unit, so patients can receive expert care closer to home.
Accessing the lab
On the research side, the RADIO lab team is focussed on discovering the fundamental biology of NETs using genomics and developing innovative new ways to diagnose and direct treatment for people with rare cancers.
Unlike numerous other cancers, NETs do not have many DNA mutations.
Instead, one of the reasons NETs grow is due to abnormal methylation. This is a process where chemical tags accumulate on DNA to switch genes 'on' or 'off', leading to cancer growth.
Methylation changes are not found on standard DNA testing, but we can identify abnormally methylated DNA by analysing a patient's cancer tissue and blood.
It is often not possible to get a tumour sample using standard surgical biopsy procedures in patients with NET, as the tumour is often inaccessible and there is a risk of life-threatening amounts of hormone being released.
Our team is working on developing non-invasive liquid biopsies to detect gene mutations as well as abnormally methylated tumour DNA in the blood, which is then read, or sequenced, to diagnose NET or identify personalised treatment possibilities.
This is part of our efforts to integrate genomic tests into the routine clinical care for NET patients.
Liquid biopsy testing for NET patients is in the early stages of use in the clinic. Our partnership means we can give patients with a rare type of NET answers through genomic testing that they would not otherwise have been able to get.
Advocacy groups have embraced the move to include patients in high-level research. Meredith Cummins, CEO of NeuroEndocrine Cancer Australia, says translational research is "so important".
"There is a great need for genomic studies so that the genetic causes of each cancer can be determined. Neuroendocrine cancers are so complex, and we need research to address the issues our NET patients encounter in their care and management."
National teamwork is the future
Our partnership between the RADIO Lab and the Peter Mac ENETs Unit is just the beginning. The pathway to better understanding this rare and complex tumour type and ultimately improving treatment requires more investment in research.
We are actively working to secure funding for a national collaboration to develop a database and biobanking program where patients with NET across Australia can have their blood or cancer samples stored to be part of future translational research.
This program would also give more Australian NET patients the opportunity to access genomic testing as part of their clinical care to help with diagnosis and treatment.
Together, we are working to provide high-quality research to improve care for current and future patients with NET.
