Study: Therapeutic drug can render cancer cells

BONN: The immune system is suppressed by the protective scent that many tumour cells spray themselves with. However, it appears that a medicine that has already been approved for other uses can render this weapon harmless.

A study from the University of Bonn and the University Medical Center Hamburg-Eppendorf that has just been published in the Journal for ImmunoTherapy of Cancer demonstrates this. The substance will now be further optimized, said the researchers. This could eventually lead to the development of novel anti-cancer medications.

A dense cloud of adenosine is present around many cancer cells. The chemical suppresses the immune system, on the one hand. At the same time, it promotes the growth of new blood vessels that feed and hydrate the tumour. Additionally, it makes sure that the cancerous cells spread to other organs and develop metastases there.

Adenosine triphosphate, or ATP for short, is used to make adenosine. It is highly secreted by tumour cells. They possess a variety of enzymes that, in a series of stages, transform ATP into adenosine.

CD39 is the name of one of these. Prof. Dr Christa Muller from the University of Bonn's Institute of Pharmacy explains that it catalyzes the initial conversion stage. "Little adenosine is generated when CD39 is blocked."

Pharmaceutical researchers are consequently looking for an active component that slows CD39 all over the world. Because cancers wouldn't be shielded from the immune system without adenosine.

Instead, Muller explains, "ATP would build up surrounding the cancer cells, which would really activate the immune response." Therefore, rather than being inhibited, the body's natural defences would be heightened.

50 approved active substances scrutinized

Pharmaceutical researchers are consequently looking for an active component that slows CD39 all over the world. Because cancers wouldn't be shielded from the immune system without adenosine. Instead, Muller explains, "ATP would build up surrounding the cancer cells, which would really activate the immune response."

Therefore, rather than being inhibited, the body's natural defences would be heightened. A total of 50 different drugs that inhibit protein kinases were authorized to treat various disorders at the beginning of the study. The research team looked at each one.

Fortunately, Schakel reports that "one of the drugs, ceritinib, likewise prevents the conversion of ATP by CD39." "We were able to demonstrate this in cultures of so-called triple-negative breast cancer cells in addition to test tubes.

These are quite challenging to treat because they frequently show little improvement with treatments." Nevertheless, Christa Muller does not think it makes sense to simply administer ceritinib as a CD39 inhibitor in certain cancers.

"After all, the active ingredient is primarily directed against a different group of enzymes; it would therefore have undesirable side effects," she says. "We now want to modify it so that it hardly inhibits protein kinases at all and instead slows down CD39 even more."

Use only in patients for whom it is worthwhile

Another therapeutic agent could be coupled with such an optimized active component. According to Prof. Muller, a member of the TRAs "Building Blocks of Matter" and "Life and Health," "classic cytostatics often dramatically decrease the immune system; CD39 blockers, on the other hand, would activate it."

"Consequently, the medications' combined effects may be much stronger." Additionally, it would be possible to determine whether cancer cells from affected patients indeed have a lot of CD39 on their surface before use. Because only then would a CD39 inhibitor regimen make sense, according to Muller.

"Therefore, you would customize the administration for each patient. In medicine, it is becoming more and more crucial to customize treatments in order to increase effectiveness."