29 January 2010
Appeared in BioNews 543Researchers in the US have found that they can predict how well breast cancer patients respond to a type of chemotherapy based on certain genes. The findings, published in the journal Nature Medicine, highlight the potential for personalised cancer therapies in the near future.
Physicians currently treat most cancers with a trial-and-error approach with two or three types of chemotherapy, each of which have their own side effects, are potentially toxic, and do not always have an effective response in the patient. In particular, a group of chemotherapy drugs called anthracyclines are given as 'adjuvant' therapy, which helps to avoid a recurrence of the tumour after surgery, but some patients seem resistant to them.
Doctors can already test for certain genes to see whether a woman's breast cancer is sensitive to oestrogen, making her a candidate for hormone-blocking drugs as part of her treatment, or whether she is HER2-positive, in which case she can be treated with an antibody. These examples account for a fraction of cases, however, and the ideal is to have a tailor-made regime for each patient, to avoid administering harmful and ineffective drugs.
The group of researchers from the Dana Farber Institute in Boston studied the DNA from breast tumour samples of 85 women who had chemotherapy with anthracyclines, and found that around one in five women had two genes on chromosome 8 that were 'upregulated', or over active. The medical records showed that these women were drug-resistant, and had seen their cancer return. When the scientists repeated the results in the laboratory on breast cancer cells, they found that the over-activity of the two genes did not protect the cells from other classes of chemotherapy drugs.
'These results suggest that tumours resistant to anthracyclines may still be sensitive to other agents', said Dr Andrea Richardson, who led the study along with Dr Zhigang Charles Wang. They and the team also applied the results to another group of breast cancer patients in Belgium, carrying out a blind study in which they correctly predicted the future effectiveness of an anthracycline the patients were treated with before their tumours were removed. 'The expression level of these genes predicted who would be resistant to the anthracycline', said Richardson, adding: 'That validated the finding in a very direct way'.
The hope is that the information will now be used to generate a genetic test to predict whether patients will be resistant to anthracyclines, so that these drugs could be avoided in their treatment. The team are now studying a range of ways to create such a test, and claim that it could be ready for clinical testing 'within the next year'. Dr Eric Winer, director of the Breast Oncology Centre at Dana Faber, said: 'while this work remains preliminary, it may ultimately help us use the anthracyclines in a much more thoughtful manner and allow us greater ability to personalise our breast cancer treatments to the tumour and the patient.'