Research How to destroy sleeper cells in tumors?

New results could lead to improved treatment of cancer

When treating cancer with the help of chemotherapy, it may initially seem as if the cancer has been completely defeated, then the surviving cancer cells multiply 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 intentionally destroyed with the help of drugs if they have defects in DNA repair.

If people have cancer, there is a risk after chemotherapy that certain sleeper cells have not 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".

In a cancer, so-called sleeper cells can escape treatment and continue to spread throughout the body. Physicians have found that certain drugs can destroy such sleeper cells if they have DNA repair defects. (Image: DOC RABE Media / fotolia.com)

Some cancer cells survive chemo and multiply again

Frequently, chemotherapy is initially promising, even if the tumor has already spread to other tissues. It may happen that doctors assume that the cancer is defeated, but then it appears again. Unfortunately, some cancer cells have survived chemotherapy in such cases. These cells then start to multiply again. Sometimes the cancer cells first respond to a new therapy, but often the cells develop a resistance to all methods of therapy, explain the experts.

Why do some tumor cells survive chemo??

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

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

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

How successful is immunotherapy??

Immunotherapy is making tremendous progress on certain types of cancer (leukemia or melanoma). In this treatment, it is achieved by strengthening the immune system that in some patients the drug-tolerant cells can be destroyed. However, the success of such a novel immunotherapy in other common tumors is relatively modest. The disadvantages of treatment are side effects and high costs.

DNA damage in tumors can lead to improved treatment

In an experiment on mice, scientists found that breast tumors with a specific defect in DNA repair can be cured using established and inexpensive chemotherapy drugs. For this, however, must first be achieved that sufficient damage of DNA in the resting tumors arise.

Results could allow for improved treatment of various cancers

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

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

DNA crosslinkers could be used to treat cancers with damaged DNA

When tested on mice, it turned out 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 bone marrow damage, which are common to most other cancer medicines. Occurring side effects can be compensated in some patients by a so-called stem cell transplantation, explain the authors. Some clinical trials in the Netherlands have already succeeded in curing some patients with already metastatic breast cancer through intensified chemotherapy, adds Rottenberg. (As)