- It is ceritinib, and it cancels the chemical protection of tumors against the immune system.
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| File image of a scientist in a laboratory. / Freepik |
A drug already approved for human use manages to leave cancer cells without their greatest weapon
One of the main reasons why many cancers can be so difficult to treat is because many tumor cells chemically protect themselves from the immune system, using a kind of 'perfume' that deactivates it.
Precisely, in recent decades, much research has been done within the promising branch of cancer immunotherapy in search of ways to counteract this weapon of cancer.
Adenosine, the secret weapon of tumors
Along these lines, a team of scientists from the University of Bonn (Germany) and the University Medical Center of Hamburg-Eppendorf (Germany) has found that a drug already approved for human use in other applications can apparently nullify this cancer resource, as detailed in an article in the specialized media BMJ. The objective, they say now, is to optimize it in order to exploit this capacity.
And it is that, as we said, many cancer cells are covered with a dense cloud composed of a substance called adenosine. On the one hand, adenosine suppresses the activity of the immune system and, on the other hand, it stimulates the formation of new blood vessels that provide oxygen and nutrients to the tumor. Likewise, it makes it possible for malignant cells to migrate to other organs and metastasize.
Adenosine is produced from adenosine triphosphate, abbreviated ATP. Tumors secrete large amounts of this substance and also carry several enzymes on the surface of their cells that transform it into adenosine. One of them is known as CD39, and it catalyzes the first step in that conversion; therefore, if it is inhibited, adenosine cannot be produced.
In fact, if ATP is not transformed into adenosine, not only is the problem of immune inhibition eliminated but, on the contrary, the accumulation of this substance alerts the immune system, which fights the tumor more fiercely.
One of fifty
It is understandable, therefore, that many researchers around the world dedicate their efforts to searching for substances capable of inhibiting the enzyme CD39. Until now, unfortunately, this search had been unsuccessful.
In this case, the team decided to opt for another strategy. In the human body, there are more enzymes that process ATP, such as protein kinases, and several substances that inhibit them are already known. Therefore, they set out to find out if any of these substances also inhibited the CD39 enzyme.
So, they took 50 of these drugs and examined their effect on CD39. One of them managed to inhibit it: ceritinib, a drug used to treat a specific type of lung cancer once it has metastasized. And not only did it do it in the test tube, but also in cultures of triple-negative breast cancer, an extremely difficult type of tumor to treat that rarely responds to therapies.
Personalized drugs
Still, the authors caution that simply giving ceritinib to any patient does not seem appropriate. And it is that the drug inhibits a long series of enzymes, which can have a series of quite severe side effects. The challenge now is to modify it so that it barely inhibits protein kinases, and instead inhibits CD39 more strongly.
Such an optimized component could be combined with other therapeutic substances, for example, some that activate the immune system against cancer even more strongly.
And, with everything, it would be necessary to analyze the suitability of each patient. Although the mechanism is fulfilled in many tumors, the CD39 enzyme does not play such an important role in all of them; in these, treatment with an inhibitor would be meaningless. For this reason, this therapeutic line may become a clear example of an increasingly strong trend in medicine: the personalization of each therapy according to the characteristics of each patient.
References
Schäkel L, Mirza S, Winzer R, et al. Protein kinase inhibitor ceritinib blocks ectonucleotidase CD39 – a promising target for cancer immunotherapy. Journal for ImmunoTherapy of Cancer 2022;10:e004660. doi: 10.1136/jitc-2022-004660
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