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Fighting cancer with methadone

Fabian SchmidtAugust 18, 2016

Certain types of chemotherapy apparently work better, when supplemented with the opioid methadone. Although, there has not been a formal clinical trial yet, first treatments with individual patients look promising.

Operation of a brain tumor. (Foto: pictue alliance/ Jan-Peter Kasper dpa/lth)
Image: picture-alliance/dpa/J. P. Kasper

It was more than eight years ago, when molecular biologist Dr. Claudia Friesen from the University of Ulm in Germany first found signs that the opioid D,L-methadone could help fight leukemia-cells and certain types of solic cancer cells. The leukemia cells died when methadone was added to an in-vitro cell culture.

Now the researcher spoke to Bavarian public broadcaster Bayerischer Rundfunk (BR) - a member of Germany's national public broadcasting system ARD - about remarkable successes in treating cancer patients.

For some years, the doctor had treated 80 patients with potentially fatal, advanced tumors with a combination of the chemotherapeutic drug temozolomide and methadone. All of the patients had previously received a very grim prognosis from their doctors, with a predicted life-expectancy not beyond summer 2015.

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All of the treated patients lived considerably longer than predicted. Some of them are still alive today, the BR reports.

About three years ago, the molecular biologist figured out the molecular mechanics behind the observed drug effect.

"With human cells in an in-vitro experiment and also in an animal experiment, we were able to show what happens to the cancer cell when we combine a conventional chemotherapy with a supplement of D,L-methadone," Dr. Friesen, the head of the forensic molecular research laboratory at Ulm University, said.

Mutual enhancement of drugs

Methadone is commonly used in substitution therapy for heroin addicts. In combination with chemotherapy, it obviously activates opioid receptors that are located on the surface of cancer cells.

"And this leads to a faster absorption of the conventional cancer drug into the cancer cell," Friesen explained.

Cancer cell(Foto: BayerHealthcare)
On the surface of certain cancer cells there are more opioid receptors than on healthy cellsImage: BayerHealthcare

"Furthermore, we were able to observe that less of the chemotherapeutic drug was being pumped out of the cell again. This means that the drug stayed inside the cancer cell longer and in higher concentrations than before."

A principle of keys and locks

The mutual enhancement of the two drugs was also influenced by one more factor: The chemotherapy apparently leads to an increase in the number of opioid-receptors on the cancer cell surface. This means even more methadone can bind to the surface of the cell.

Deutschland Dr. Claudia Friesen
Dr. Claudia FriesenImage: Universitätsklinikum Ulm

"This is like a principle of locks and keys," the molecular biologist said. "The higher the number of matching keys and the higher the number of doors with locks, the higher the possibility that one of them will open. This results in the death of the cancer cell."

Healthy cells, on the other hand, do not get damaged because they have a very small number of receptors on their surface. In their case, the signaling cascade - which eventually results in the cell's death - doesn't even get started.

But tests have shown that drugs known as opioid antagonists effectively interrupt the principle of keys and locks. "Using an opponent drug of D,L-methadone functions like sticking glue or bubble gum into the lock: the key won't work anymore," Friesen explains.

The findings cannot be applied to other forms of cancer, such as pancreatic cancer, breast cancer, ovary cancer or prostate cancer, Friesen stressed. [note from the editors: since original publication this article has been out of date. The German cancer foundation "Deutsche Krebshilfe" announced in July 2017 that "use of methadone as cancer medication outside of clinical trials is not justified" please refer to an oncologist for any questions - updated November 2nd 2017].

Not a full clinical trial yet

Dr. Friesen was able to conduct her experiments thanks to project funding that she received from the German cancer foundation (Deutsche Krebsstiftung) in 2009. The treatment of the 80 patients does not have the full status of a formal clinical trial, though.

Therefore, the first experiences with the treatment are not considered scientific proof of the supportive effect of methadone in chemotherapy yet - according to the rules of drug licensing.