How cancer cells resist radiotherapy

  • Wellness
  • Saturday, 27 Jun 2020

Santer looks at cancer stem cells that have survived a process mimicking radiotherapy in the lab. — FWF

Cancer stem cells are a cell type that was previously little known, but are now a controversial topic widely discussed in current cancer research.

A popular research subject, stem cells are precursor cells for various body cell types.

They play an important role in embryonic development, as well as in tissue maintenance.

Many types of cancer also involve a type of cell that shares many properties with stem cells.

While regular stem cells are precursors of healthy body cells, cancer stem cells are precursors of different types of cancer cells.

Normal stem cells and cancer stem cells therefore have many common aspects that are of interest to researchers.

One important factor is that cancer stem cells are resistant to irradiation and prevent the effective treatment of many types of cancer.

“Cancer stem cells are a very contentious issue,” explains molecular biologist Frédéric Santer from the Department of Urology at the Medical University of Innsbruck, Austria.

“It is still unclear whether they originate from normal stem cells or from differentiated, degenerate cells that are regressing.”

Such processes are difficult to detect in living organisms.

However, he points out that the similarity of their properties is undisputed, in particular, their resistance to therapy.

The latter is a problem because cancer stem cells that survive therapy are held responsible for the recurrence of cancer in cured individuals.

The resistance of stem cells can be explained by natural necessities.

A certain resistance to environmental influences such as chemicals is useful for them, he says.

“Regular cells have mechanisms that trigger cell death when DNA (deoxyribonucleic acid) is damaged.

“Stem cells, on the other hand, are designed to regenerate damaged tissue.

“So it makes sense that they survive in situations where other cells die,” he explains.

How they manage to do that has not, however, been sufficiently researched.

“But that is enormously important for cancer therapy,” emphasises Santer, for whom this information deficit was inspiration for his research project, funded by the Austrian Science Fund (FWF).

“We wanted to look at what happens at the level of genes during radiotherapy.”

Two problems discovered

In order to do that, Santer’s team used tissue samples from patients with prostate cancer.

Unless it is very advanced, the primary therapy for prostate cancer is the surgical removal of the prostate.

This meant that the researchers had direct access to cancer cells from patients.

After surgery, the removed tissue is routinely sent to the pathology department, where a report is drawn up. Only then can Santer’s team use it for research.

“It is not easy to cultivate these cells in the laboratory,” he explains.

“The process is complex and we had to invest a lot of time before we were able to create optimum conditions for the actual experiment.”

After successful cultivation, the cell samples were irradiated in line with a protocol for radiotherapy that patients receive.

“Irradiation causes DNA damage. If this damage is too extensive to be corrected by repair mechanisms, the cell normally dies,” he explains.

However, some cells survived the irradiation process.

These cells were subsequently compared with the original tissue.

The researchers were particularly interested in gene expression, which refers to the process by which genes are translated into protein structures.

In the process, the genetic code in the cell nucleus is read and converted into RNA (ribonucleic acid).

An analysis of this RNA provides information about the processes taking place in a cell.

“We found that two important processes of the radio-resistant cells are weakened,” Santer shares.

One is the production of proteins that are regulated by interferons, which is used by the immune system to fight viruses and cancer cells.

In the irradiated cells, the production of proteins in the interferon cell-signalling pathway was inhibited.

This effect was also recently confirmed by another international study on breast cancer stem cells.

Another disrupted process was the cell cycle arrest, which involves a mechanism that prevents cell division in the presence of damaged DNA.

This mechanism was disrupted as certain proteins required for the process were not produced in sufficient quantities.

“This actually constitutes a malfunction, but it helps the cell to survive because it can continue to reproduce without constraint despite the DNA damage,” he says.

Both effects are problematic because they promote the development of cancer.

However, the more detailed understanding of these effects can now serve as a starting point for new cancer therapies, according to Santer. – FWF

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