Tuber agaric against pancreatic cancer

In pancreatic carcinoma therapy with tuberous agaric is promising

Pancreatic cancer is considered to be particularly insidious and difficult to cure. Scientists from the German Cancer Research Institute (DKFZ) in Heidelberg have now successfully used amanitin, the poison of the tuberous agaric fungus, against pancreatic carcinoma in mice.

Often poor prognosis for pancreatic cancer
Pancreatic cancer (medical: pancreatic cancer) is difficult to treat. As a rule, the diagnosis is made very late because there are hardly any complaints in the initial stage of the disease. It is only later that classic symptoms such as jaundice, abdominal pain, loss of appetite, underweight, nausea and vomiting, as well as a possible feeling of pressure in the upper abdomen, can occur if, from a medical point of view, treatment success can hardly be achieved. However, the pain can have various causes, so that an exact diagnosis is necessary. The symptoms usually only appear when the pancreatic carcinoma has already spread to neighboring organs such as the intestine or stomach. The tumors then cause the symptoms mentioned. Pancreatic cancer itself usually causes almost no noticeable symptoms in patients.

The tumor can only be operated on in about five percent of the diagnoses. One of the prominent victims was Apple founder Steve Jobs, who died of cancer in the past year after seven years of suffering. The five-year chance of survival after an initial diagnosis is less than six percent for men and only eight percent for women. Patients generally respond very poorly to chemotherapy. The news from the DKFZ is all the more gratifying: German researchers have reported first successes in using the tuber agaric mushroom in the fight against pancreatic cancer.

Poison from the tuber agaric acts inside the cancer cell
The DKFZ scientists succeeded in coupling the amanitin to an antibody (anti-EpCAM) that can identify a cancer-typical target molecule. The antibody acts as a control element that specifically transports the poison to the cancer cells. In this way, pancreatic tumors completely disappeared in mice.

The tuber agaric is very similar to the Parasol. It contains one of the deadliest poisons in the plant kingdom. Amanitin, its poison, kills every cell without exception. It doesn't matter whether she is healthy or has cancer. Together with the biochemist Heinz Faulstich, the immunologist Gerhard Moldenhauer developed a mechanism by which the fungal poison only destroys cancer cells and spares healthy cells.

Antibody transports the poison
To achieve this, the poison must be transported to the tumor cells. An antibody acts as a means of transport, which with its special gripper arms is able to dock onto the cancer-typical cell surface protein EpCAM. The mushroom poison is chemically stable coupled to its transporter. A single administration of the antibodies inhibited cancer growth in mice that had been implanted with human pancreatic cancer. When injected twice at higher doses, the tumor even completely disappeared in 90 percent of the animals. Fortunately, the mice showed no organ damage despite the high dose of the poison.

EpCAM, a characteristic membrane protein of epithelial cells, was selected by the scientists as the recognition structure of the cancer cells. All internal and external interfaces of the body are lined with this cell type. Most malignant tumors develop from epithelial tissues. EpCAM is formed in large quantities by many tumors such as breast and ovarian cancer, pancreatic cancer, bile duct cancer or head and neck cancer, which is often accompanied by a very poor prognosis of the disease. Therefore, the researchers chose EpCAM as the target structure for attacking the tumor cells.

“Treatments with uncoupled antibodies against EpCAM have already been clinically tested (…). You should attack cancer with the weapons of the immune system alone, but they have proven to be clinically ineffective, "explains Gerhard Moldenhauer." Our amanitin-coupled antibody, on the other hand, has a much higher potential to destroy cancer cells. "

Four to eight poisonous molecules per antibody
There are about four to eight poisonous molecules on each antibody. Amanitin is particularly suitable because it is so small that it is not recognized by the immune cells as an intruder. On the other hand, it is so robust that it can be chemically coupled well. “The cancer cell and the docked antibody must regularly bring the target molecule inside the cell, because only there can the poison work. The poison must separate from the antibody inside the cell, otherwise it will not be effective, "explains the immunologist.

In initial studies, a similar strategy has shown success in breast cancer patients. T-DM1 is an antibody conjugate that is currently being developed against breast cancer. It consists of the monoclonal antibody Herceptin and the chemotherapy drug Mersantine. It has hardly any side effects.

Causes of pancreatic cancer
Despite many years of active research, the exact cause of pancreatic cancer is still largely unknown. Recent scientific studies indicate that the first cell mutations often occur 20 years before the disease actually occurs. It is therefore not surprising, according to British researchers, that the survival rate of the disease has hardly improved in the past 40 years. At the time of diagnosis, pancreatic cancer is usually extremely aggressive and treatment is hardly promising.

In addition to genetic predispositions, long-term smoking, alcohol habit, severe obesity, diabetes, cystic changes and chemical pollutants are considered to be very favorable for the development of cancer. As with other cancers of the digestive organs, constant irritation, such as long-lasting inflammation of the pancreas, can increasingly lead to the degeneration of the body's own cells. However, genetic disposition is now considered the main cause among experts. (ag)

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Pancreatic cancer has been developing for years
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