Combination therapy can effectively inhibit tumor growth

Researchers at the Paul Scherrer Institute PSI have tested different methods to verify their effectiveness in the fight against certain types of cancer. They found that a combination of two preparations was much more effective than treatment with just one of the two active substances. They published their findings today in the medical journal Pharmaceutical.

A combination of an active substance based on rapamycin and a peptide coupled to the radionuclide lutetium can effectively inhibit tumor growth. This is the key result of a study carried out by researchers at the Paul Scherrer Institute in collaboration with colleagues from the University of Basel and ETH Zurich. The study builds on previous radiopharmaceutical research undertaken at PSI.

To treat tumors with radiopharmaceuticals, researchers couple radionuclides with certain molecules that attach particularly well to tumor cells and are then absorbed by these cells. In this particular case, they use mini-gastrin associated with the radionuclide lutetium-177. The radioactive mini-gastrin attaches to a specific receptor on the surface of the membrane of the cancer cell, from where the drug is transported inside the cell.

The problem is that part of the radiopharmaceutical that binds to the receptor has been developed from gastrin, a naturally occurring substance found in the human body. It is generally responsible for releasing stomach acid to aid in the digestion of food. Healthy gastric cells therefore also produce the receptor, so that the radiopharmaceutical also attaches to it. Healthy stomach cells also absorb the drug and can therefore also be damaged.

Manipulation of tumor cells

Michal Grzmil, cancer biologist at the PSI Center for Radiopharmaceutical Sciences, explains: “The idea behind the new combination therapy is that the rapamycin substance only manipulates cancer cells so that they produce more receptor molecules and thus absorb larger amounts of radionuclide. The aim is to ensure that the dosage of the radiopharmaceutical absorbed by the stomach does not produce excessive side effects.

After docking with the cancer cell, lutetium radiation destroys the DNA of the cells, in the best case killing the cells and having a therapeutic effect on the tumor.

Although this type of therapy is already used in practice, this new discovery considerably improves its effectiveness. During their research, scientists found that when using a combination of the active substance rapamycin and the radiopharmaceutical, the level of radiation entering the tumor is much higher, while the level in the stomach remains the same.

We have determined that this allows us to inhibit tumor growth by about half compared to administration of rapamycin alone. “

Martin Béhé, Head, Pharmacology Group, PSI Center for Radiopharmaceutical Sciences

Treat thyroid cancer

This method is particularly suitable for the treatment of medullary thyroid cancer (CMT) and is currently the subject of clinical trials carried out in close collaboration with Debiopharm International, a pharmaceutical company based in Lausanne, and the University Hospital of Basel. TCM is the third most common type of thyroid cancer. Although it is quite rare, accounting for less than ten percent of all thyroid cancers, it ranks among the particularly aggressive strains because it metastasizes easily. About a quarter of these tumors are due to hereditary factors, so sometimes children or young adults are even affected.

Lutetium-177 offers several advantages

The isotope lutetium-177 offers several advantages for treating this type of tumor: it emits both beta and gamma radiation. Beta radiation travels only a few millimeters in the body. As soon as the radiopharmaceutical kicks in, it can directly destroy the tumor without damaging surrounding tissue. Gamma radiation, on the other hand, leaves the body again and can be detected and measured by a gamma camera. Based on these readings, the camera produces an image showing the buildup of the radioactive substance in the body and showing the spread of medullary thyroid cancer.

“We still have to optimize the method through clinical trials,” specifies Martin Béhé. But he is optimistic that these trials will corroborate the results to date and believes that the treatment will be widely available in a few years.

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