Text | Zhang Yefan Pineapple
Today, February 24 is the birthday of Apple founder Steve Jobs. As we all know, Jobs died after 8 years of cancer. Many people think that he has malignant pancreatic cancer, and then guess that it must be because he is very rich, so he can live so long, after all, the average survival time of pancreatic cancer is less than 1 year.
In fact, no, Jobs did not get pancreatic cancer, but pancreatic neuroendocrine tumor (abbreviated as PNET), which is a type of pancreatic tumor with a lower degree of malignancy and a better survival prognosis.
Today we will talk about this relatively rare tumor.
You must first ask, what exactly is a pancreatic neuroendocrine tumor?
Neuroendocrine tumors are a general term for a class of tumors that are produced by the deterioration of mutations in hormone-producing cells. It can occur in the pancreas, but it can also occur in the gastrointestinal tract, liver and gallbladder, or lungs. If it occurs in the pancreas, it is called a pancreatic neuroendocrine tumor.
Compared with many malignant tumors, most neuroendocrine tumors are much more docile, grow slowly, usually progress in years, and even if metastases occur, long-term survival can be obtained through surgery combined with drug therapy, and the 5-year survival rate is close to 50%. Clinically, doctors can remove or shrink it using different treatments, or improve clinical symptoms through treatment. Of course, there are also some with a higher degree of malignancy, called neuroendocrine cancer, which can spread to other parts of the body, causing more serious consequences.
What are the symptoms of pancreatic neuroendocrine tumors?
Because neuroendocrine tumors come from hormone-producing cell variants, they often lead to hormonal imbalances. Patients may experience diarrhea, dizziness, rapid heartbeat, headache, hunger, rash, abdominal pain, sweating, weight loss, and other symptoms.
Images are from the public image gallery
Doctors who want to diagnose neuroendocrine tumors need to do a series of tests, such as the following:
Blood and urine tests: used to check hormone levels in the body.
CT scan: used to determine the location, size, and metastasis of the tumor.
MRI: It can better display organs such as the pancreas, liver, and biliary tract, providing clearer images.
Octreotide scan: A small amount of radiopharmaceuticals are injected into the body through a vein, which contains an ingredient called octreotide, which can specifically adhere to the surface of most neuroendocrine tumors, and through the scan, the tumor cells in the body may be visible.
Ga68-PETCT: A special radioactive isotope PET-CT scan designed based on the expression of somatostatin receptors on the surface of many neuroendocrine tumors, which is currently the most sensitive and detectable means, especially suitable for neuroendocrine tumors with unknown primary focus
Biopsy: A small piece of tissue is removed from the suspected lesion by puncture and examined under a microscope to see if there are any tumor cells, as well as the specific type of tumor cells.
Molecular testing: Biopsy samples are genetically tested, protein tested, and other tests are performed to identify specific tumor subtypes to determine which treatment to choose.
Pancreatic neuroendocrine tumors are less malignant, but clinically difficult to cure completely. At present, surgery is still the most common treatment for many neuroendocrine tumors, especially those that are benign and have not yet spread. Radiotherapy and chemotherapy are also often used when needed.
In recent years, with the popularization of gene sequencing, the treatment of pancreatic neuroendocrine tumors has begun to develop in the direction of precision medicine.
When Jobs fell ill, there were hardly any effective drugs. In the case that sequencing was still relatively expensive, Jobs spent money on genome sequencing of his own tumor at that time, hoping to find new therapeutic targets and more effective treatment options. Although the results were not ideal, and no particularly good targets and drugs were found, this was one of the earliest attempts to use genetic testing to carry out personalized diagnosis and treatment of tumors.
In 2011, the year of Jobs's death, the genetic mutation profile of pancreatic neuroendocrine tumors was published, and scientists found that MEN1 was the gene with the highest frequency mutation in such tumors, and more than 50% of tumors had MEN1 mutations.
At the same time, some people in the world are born with MEN1 mutations, so they are likely to get a disease called "multiple endocrine gland tumor syndrome type I( also called Wehrmer syndrome)."
As you may know, if you are born with BRCA mutations, such as Angelina Jolie, you can reduce the risk of breast cancer by removing the breast through preventive surgery, but if you carry a MEN1 mutation, can you also remove it early?
No way!
Because the tumor that this mutation may bring is located in the pituitary gland, parathyroid gland, pancreas and other organs, the function is too important to be cut casually.
So far, there are no good drugs that can prevent tumors in patients with Weermer syndrome, and there is no treatment plan for MEN1 mutant tumors, but doctors and scientists have been working hard.
In the past two days, the team of Professor Jiao Yuchen and Professor Zhao Hong from the Cancer Hospital of the Chinese Academy of Medical Sciences has published an interesting paper confirming that MEN1 mutant tumors rely specifically on a gene called DHODH. Cell tests have shown that if the activity of the DHODH gene can be suppressed, the growth of such tumors will be limited.
Screenshot of the cover of the paper
Interestingly, there is already a DHODH inhibitor on the market, and that is leflunomide, a drug that has been on the market for a long time as a major treatment for rheumatoid arthritis. In animal models, leflunomide can indeed significantly inhibit tumor growth with MEN1 mutations. Since leflunomide itself has been on the market for many years and has no problem with safety, the research team quickly launched a clinical trial using leflunomide for the treatment of MEN1 mutant tumors.
The article also reported that 3 patients who failed first-line treatment maintained progression-free survival after treatment with leflunomide, and patients had clinical improvements such as disappearance of pleural fluid and disappearance of PET-CT signal. At present, the clinical trial has enrolled 7 patients, the treatment time has reached 6-14 months, and there has been no progression of the disease and no serious side effects.
Animal models also showed that for mice born with MEN1 mutations, if flumeter was used from 6 months old (equivalent to 18-20 years old in humans), the incidence of tumors could be greatly reduced from 65% to 5%, suggesting that leflunomide, or other DHODH inhibitors, may be used in the future to prevent tumors in patients with Weermer syndrome.
It is very good to see that China can have such a good original translational study, which provides a new idea for the treatment of MEN1 mutant tumors and the prevention of Weermer syndrome, and hopes that follow-up clinical trials can bring more good news.
In summary, pancreatic neuroendocrine tumors are not pancreatic cancers, but a type of neuroendocrine tumor. Neuroendocrine tumors are a general term for tumors with neuroendocrine function, which can occur in many parts, have different functions, and can cause a variety of symptoms, which brings great challenges to their diagnosis and treatment. If you suspect or diagnose such tumors, it is strongly recommended that you go to a specialist hospital and a doctor to develop the most suitable diagnosis and treatment plan for yourself.
I wish you all good health! Hail to life!
Zhang Yefan
Cancer Hospital, Chinese Academy of Medical Sciences
Deputy Chief Physician, Department of Hepatobiliary Surgery
*This article aims to popularize the science behind cancer and treatment, not drug promotional materials, let alone treatment plan recommendations. For guidance on treatment options, visit a regular hospital.
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