Chemotherapy 'encourages cancer' claim researchers

Behind the Headlines

Monday August 6 2012

Some chemotherapy drugs were damaging the DNA of healthy cells

“Chemotherapy can actually boost the growth of cancer cells, making the disease harder to fight,” the Metro has gloomily reported.

The newspaper's claim focuses on some research that could explain a frustrating problem in cancer treatment: the majority of advanced cancers, where the cancer has spread to multiple parts of the body (metastatic cancer), become resistant to chemotherapy treatment. This means that most metastatic cancers are incurable.

This news is based on a study looking at cancer tissue and cells in the laboratory and in mice. Rather than looking at the effects of cancer treatments on the tumours themselves, they looked at the effect on the normal cells around the tumour. The study found that after chemotherapy or radiation these cells produced more of a protein called WNT16B, which actually helped the cancer cells to divide and become more invasive.

This interesting research has identified a way in which cancer treatment resistance may be induced by the effects of the chemotherapy treatment itself on the cells surrounding the tumour.

While this may sound like bad news, gaining a greater understanding of how this resistance may come about is very valuable. It could allow researchers to develop ways of stopping this resistance from happening, and improve the results of cancer treatments. 

 

Where did the story come from?

The study was carried out by researchers from the Fred Hutchinson Cancer Research Center and other research institutes in the US. It was funded by the US Department of Defense, the National Cancer Institute, the Pacific Northwest Prostate Cancer SPORE and the Prostate Cancer Foundation.

The study was published in the peer-reviewed journal Nature Medicine.

The newspapers generally covered the research well, although some headlines may give the impression that chemotherapy was found to do more harm than good. In fact, the study just looked at trying to explain why tumours may gain resistance to chemotherapy, and does not alter what is known about its benefits.

 

 

What kind of research was this?

This was laboratory and animal research looking at how cancers acquire resistance to chemotherapy. The researchers say that resistance to chemotherapy is a major reason why cancer treatments fail.

Previous research has suggested that the sensitivity of tumour cells in the laboratory to a chemotherapy drug does not accurately predict whether the tumour they come from will be sensitive. This suggests that it isn’t just the cancer cells themselves which determine chemotherapy sensitivity.

Chemotherapy treatments often work by damaging the DNA of cells, and although they have more of an effect on cancer cells, they can also damage the DNA of normal cells. The current study looked at whether chemotherapy-induced DNA damage to the non-cancerous cells around a cancerous tumour could contribute to the latter's resistance to chemotherapy.

 

What did the research involve?

The researchers obtained tissue samples from men with prostate cancer before and after chemotherapy and assessed cells in the surrounding non-cancerous prostate tissue for DNA damage.

To investigate the effects of this DNA damage, they treated cells from this tissue with different cancer treatments (chemotherapy drugs and radiation) in the laboratory to induce DNA damage. They then looked at which genes’ activity had been most affected by the DNA damage (the genes that were much more or much less active after the DNA damage). They focused on genes that were at least 3.5 times more active after chemotherapy or radiation.

The researchers then tested whether these genes were also more active in the prostate tissue they collected from patients after chemotherapy, in cells from other types of cancers treated (either in the laboratory or in patients, and in tissue from mice treated with chemotherapy.

The researchers assessed whether the level of activity of the gene(s) of interest was associated with the likelihood of prostate cancer recurrence. They carried out a range of experiments on cells in the laboratory and in mice to see how the gene(s) of interest might contribute to cancer recurrence.

Finally, they carried out experiments to see if the WNT16B protein could actually affect cancer cell response to chemotherapy.

 

What were the basic results?

The researchers found DNA damage to two types of cells in the normal prostate tissue that would surround the tumour: fibroblasts and smooth muscle cells.

Treating fibroblasts from primary prostate cancer tissue with chemotherapy or radiation in the lab also caused DNA damage. After this treatment and DNA damage, several genes became more active than before. This included the gene encoding a protein called WNT16B, which is secreted by the fibroblasts and could therefore affect neighbouring cells. The gene for WNT16B was between 8 and 64 times more active after the different cancer treatments. Similar results were found in:

  • prostate tissue collected from patients before and after chemotherapy
  • fibroblast cells from breast and ovarian cancers treated with cancer treatments in the laboratory or from actual patients
  • prostate, ovarian and mammary tissue from mice treated with chemotherapy

The more WNT16B protein produced in the prostate tissue after chemotherapy, the more likely the cancer was to come back after treatment.

Further experiments showed that the WNT16B protein promoted cancer cell division and the ability of the cancer cells to invade tissue, which helps tumours to grow and spread.

Prostate cancer cells exposed to the secretions from fibroblasts genetically engineered to produce WNT16B protein were less responsive to chemotherapy in the laboratory. Prostate and breast cancer tumours transplanted into mice were also less responsive to chemotherapy if they had been transplanted with fibroblasts genetically engineered to produce the WNT16B protein.

 

How did the researchers interpret the results?

The researchers concluded that their findings indicate a way that cancer treatments may enhance treatment resistance through effects on the cells around the tumour (the tumour microenvironment).

 

Conclusion

This interesting research has identified a way in which cancer treatment resistance may be induced by the effects of the cancer treatment itself on the cells surrounding the tumour. These results come from assessments mainly on cells in the laboratory and in mice, but are supported by assessments of tumour tissue from patients with prostate, ovarian and breast cancer.

Tumours gaining resistance to cancer treatments is a major reason for treatment failure, so a greater understanding of how this resistance may come about is very valuable. The researchers hope they will be able to develop ways of stopping this resistance from happening, and improve cancer treatment results. This may involve looking at different ways of delivering existing treatments to minimise this response, or developing new drugs that either block this response or do not trigger it.  

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links to the headlines

'Chemotherapy can "encourage cancer", claims new research'. Metro, August 5 2012

'Chemotherapy can backfire by "encouraging cancer growth"'. Daily Mail, August 6 2012

'Chemo "undermines itself" through rogue response'. BBC News, August 6, 2012

Links to the science

Sun Y, Campisi J, Higano C et al. Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nature Medicine. Published online August 5 2012

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The 1 comments posted are personal views. Any information they give has not been checked and may not be accurate.

BGT said on 07 August 2012

It's interesting to see in this article that 'resistance' is actually a vague term. As this research suggests, the fact that the cancer doesn't respond to treatment does not mean it has developed 'resistance'. In this example, it simply means that other factors are promoting its growth.

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Analysis by Bazian

Edited by NHS Choices

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