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DNA damage during chemotherapy can trigger treatment resistance

13 August 2012
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'.
SOURCES & REFERENCES
Chemotherapy can backfire by 'encouraging cancer growth', new research claims
Mail Online |  6 August 2012
Chemo 'undermines itself' through rogue response
BBC News |  6 August 2012
Exposing the Roots of Chemotherapy Resistance
Genetic Engineering and Biotechnology News |  6 August 2012
Researchers discover new mechanism behind resistance to cancer treatment
Eurekalert! |  5 August 2012
Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B
Nature Medicine |  5 August 2012
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