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Research: How can sleeper cells be destroyed in tumors?


New results could lead to improved treatment for cancer

When treating cancer with the help of chemotherapy, it may appear that the cancer has been completely defeated, then the surviving cancer cells multiply again and the disease breaks out again. So-called sleeper cells often survive the therapy and spread again after the treatment. However, these cells can be destroyed with the help of drugs if they have defects in the DNA repair.

If people have cancer, after chemotherapy there is a risk that certain sleep cells may not have been affected by the treatment. This causes the cancer to spread again. Researchers found that so-called sleeper cells can be destroyed if they have specific defects. This could lead to more effective treatment for cancer. The scientists published the results of their study in the journal "Clinical Cancer Research".

Some cancer cells survive chemotherapy and reproduce

Chemotherapy is often promising, even if the tumor has spread to other tissues. Doctors may assume that the cancer has been defeated, but then it reappears. In such cases, unfortunately, some cancer cells have survived chemotherapy. These cells then start to multiply again. Sometimes the cancer cells first respond to a new therapy, but often the cells develop resistance to all methods of therapy, the experts explain.

Why do some tumor cells survive chemotherapy?

The scientists wanted to find out why individual tumor cells sometimes survive the therapy. In their investigation, the researchers then found that so-called sleeper cells are able to escape chemotherapy. These cells survive chemotherapy by taking a short growth break. The cells are then not affected by the treatment because chemotherapy is directed primarily against active, dividing tumor cells. When the therapy is stopped, the sleeper cells start to multiply again. However, if such sleep cells have a specific mutation, they can be destroyed with the help of medication, the scientists emphasize.

How can we destroy so-called drug-tolerant cells?

If the tumor cells have survived such chemotherapy, they are called drug-tolerant cells, explains author Sven Rottenberg from the Vetsuisse Faculty at the University of Bern. In this case, of course, the question arises how such cells can be destroyed.

What success does immunotherapy achieve?

Immunotherapy is making tremendous progress in certain types of cancer (leukemia or melanoma). With this treatment, strengthening the immune system means that the drug-tolerant cells can be destroyed in some patients. The success of such a novel immunotherapy for other frequently occurring tumors is, however, relatively modest. The disadvantages of the treatment are side effects and high costs.

DNA damage in tumors can lead to improved treatment

In an experiment on mice, the scientists found that breast tumors with a specific defect in DNA repair can be cured if established and inexpensive chemotherapy drugs are used. To do this, however, it must first be ensured that there is sufficient damage to the DNA in the resting tumors.

Results could enable improved treatment for various types of cancer

The new results could significantly improve the therapy of breast, ovarian and prostate cancer in the future. Nowadays, cancer is no longer classified and treated according to the origin of the tissue, but certain analyzes are also carried out to find individual mutations that can be used for therapy, the scientists explain. Such analyzes include, for example, the sequencing of genes and a search for certain proteins, the researchers say.

Defects in DNA repair arise from a malfunction of proteins, which are used to repair DNA damage in healthy body cells. If such proteins are inactive, the result is faulty repair. Sleeping cells with defects in DNA repair are susceptible to certain substances that can damage DNA. Such drugs affect not only cancer cells, but also healthy cells. Compared to normal cells, tumor cells are significantly more sensitive to this type of treatment because they are unable to repair the damage effectively.

DNA crosslinkers could be used to treat cancers with damaged DNA

When testing on mice, it emerged that so-called DNA crosslinkers can be used very effectively for treatment. Such DNA crosslinkers have been available on the market for a long time. So far, however, they have not been used to treat cancers with damaged DNA repair.

Treatment with DNA crosslinker has strong side effects

Unfortunately, these DNA crosslinkers have strong side effects, such as damage to the bone marrow, which also occurs with most other anti-cancer drugs. The side effects that occur in some patients can be compensated for by a so-called stem cell transplant, the authors explain. In some clinical trials in the Netherlands, intensive chemotherapy has already been able to cure some patients with already metastatic breast cancer, added Rottenberg. (as)

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