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DNA damage during chemotherapy can trigger treatment resistance

13 August 2012

By Dr Caroline Hirst

Appeared in BioNews 668

Chemotherapy can produce a rogue response that eventually leads to tumours becoming resistant to treatment, scientists have found.

A study published in the journal Nature Medicine shows how DNA damage from anti-cancer drug therapy can cause healthy cells to produce a protein that helps cancer cells to resist treatment.

Around 90 percent of patients with solid cancers develop resistance to chemotherapy. The finding may help scientists develop drugs designed to control or avoid this rogue response and thereby enhance treatment effectiveness.

Tumour cells are surrounded by neighbouring healthy cells known as the tumour microenvironment. Researchers from a cancer research centre in Seattle in the USA showed that when these neighbouring cells have their DNA damaged during chemotherapy, they produce up to 30 times the normal amount of a protein called WNT16B.

WNT16B stimulates the growth and spread of the cancer cells and helps them develop resistance to treatment – a newly discovered function for this protein.

The human prostate, breast and ovarian cancer cells studied all showed an increase in WNT16B production. When researchers looked specifically at prostate cancer patients given chemotherapy, they found that increased levels of WNT16B in the tumour microenvironment were associated with an increased likelihood of cancer recurrence.

'Cancer therapies are increasingly evolving to be very specific, targeting key molecular engines that drive the cancer rather than more generic vulnerabilities, such as damaging DNA', said Dr Peter Nelson, a senior author of the study. 'Our findings indicate that the tumour microenvironment also can influence the success or failure of these more precise therapies'.

Professor Frances Balkwill, a Cancer Research UK expert on the tumour microenvironment told BBC News: 'This work fits with other research showing that cancer treatments don't just affect cancer cells, but can also target cells in and around tumours'. She added that 'the next step is to find ways to target these resistance mechanisms to help make chemotherapy more effective'.


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28 May 2012 - by James Brooks 
A drug that mimics broken strands of DNA and pushes treatment-resistant cancer cells to autodestruct has produced encouraging results in a first clinical trial. The medicine, DT01, is the forerunner for a new class of drug developed by researchers at the Institut Curie in Paris...
14 November 2011 - by Dr Louisa Petchey 
A new genetic test that will help to tailor drugs to cancer patients' individual tumours has been successfully trialled in the US...
16 May 2011 - by Dr Jay Stone 
US scientists have designed a genetic test which could predict how a patient with breast cancer responds to chemotherapy. Researchers say the test, which works for those with certain newly diagnosed forms of cancer, could help women avoid unnecessary chemotherapy....

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