Tuberous toadstool for pancreatic cancer

In pancreatic cancer therapy with tuberous mushroom promising

03/04/2012

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

Commonly poor prognosis for pancreatic cancer
Pancreatic cancer (medical: pancreatic carcinoma) 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. Only in the later stages can it come to the 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, if from a medical point of view hardly more treatment successes can be achieved. However, the pain can have multiple causes, so an accurate diagnosis is necessary. The symptoms usually do not appear until the pancreatic carcinoma has already passed over to neighboring organs such as the intestines or the stomach. The tumors then cause the aforementioned complaints. The pancreatic cancer itself usually causes almost no noticeable symptoms in patients.

Only in about five percent of the diagnoses, the tumor is still operable. Among the prominent stakeholders included Apple founder Steve Jobs, who died after seven years of suffering last year from the consequences of cancer. The five-year chance of survival after initial diagnosis is less than six years for men and only eight percent for women. Patients usually respond to chemotherapy very badly. All the more encouraging is the report from the DKFZ: German researchers have reported first successes in the use of tuberous mushroom in the fight against pancreatic cancer.

Poisonous mushroom poison acts inside the cancer cell
The scientists of the DKFZ succeeded in coupling the amanitin to an antibody (anti-EpCAM), which can identify a cancer-typical target molecule. The antibody acts as a control that specifically transports the toxin to the cancerous cells. In this way, pancreatic tumors completely disappeared in mice.

The tuberous toadstool is very similar to the parasol. It contains one of the deadliest poisons in the plant kingdom. Amanitin, his poison, kills every cell without exception. It does not matter if it is healthy or cancerous. Immunologist Gerhard Moldenhauer and biochemist Heinz Faulstich developed a mechanism that uses fungal poison to destroy only cancer cells and spare healthy cells.

Antibody transports the poison
To achieve this, the poison must be transported into the tumor cells. The transport agent is an antibody which, with its special gripping arms, is able to dock on the cancer-typical cell surface protein EpCAM. The fungus toxin is chemically coupled to its transporter. Already a single administration of the antibodies inhibited cancer growth in mice implanted with human pancreatic cancer. When injected twice with higher doses, the tumor even disappeared completely in 90 percent of the animals. Fortunately, the mice showed no organ damage despite the high dosage of the poison.

EpCAM, a characteristic membrane protein of epithelial cells, has been selected by scientists as the recognition structure of 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 produced in large quantities by many tumors such as breast and ovarian cancer, pancreatic cancer, bile duct carcinoma or head and neck cancer, which is often associated with a very poor prognosis of the disease. Therefore, the researchers chose EpCAM as the target for attacking the tumor cells.

„Treatments with uncoupled antibodies to EpCAM have already been clinically proven (...). They should attack the cancer alone with the weapons of the immune system, but have proved to be clinically ineffective, "explains Gerhard Moldenhauer. „Our amanitin-coupled antibody, on the other hand, has a far greater potential for destroying cancer cells. "

Four to eight poison molecules per antibody
Each antibody contains about four to eight poison molecules. 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 well coupled. „The cancer cell must regularly bring the target molecule together with the docked antibody into the cell, because only there can act the poison. Inside the cell, the poison has to dissolve away from the antibody, otherwise it is not effective, "explains the immunologist.

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

Causes of pancreatic cancer
Despite many years of active research, the exact cause of the development of pancreatic cancer is still largely unknown. Recent scientific studies indicate that the first cell mutations often occur 20 years before the actual onset of the disease. It is therefore not surprising, according to British researchers, that the survival rate of the disease has barely improved over the last 40 years. At the time of diagnosis, pancreatic cancer is usually very aggressive and treatment is unlikely to be successful.

In addition to genetic dispositions, smoking, alcoholism, overweight, diabetes, cystic changes and chemical pollutants are a long-standing factor in the development of cancer. As with the other cancers of the digestive organs, constant irritation such as prolonged pancreatitis can increasingly lead to degeneration of the body's own cells. The genetic disposition is now regarded by experts as the main cause. (Ag)

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Picture credits: Marion