Tamoxifen resistance may be reversible
Resistance to breast cancer drug tamoxifen could be reversed by adding a simple chemical to the drug, say researchers.
Tamoxifen has an initial success rate of 50 per cent when used to stop breast cancer returning after surgery, but can lose its effectiveness over time.
"Tamoxifen has been extremely important in the management of breast cancer," said director of the US National Cancer Institute (NCI) Dr John E. Niederhuber.
"Being able to overcome resistance would be an important advance."
In the study, led by William Farrar, PhD, of NCI's Center for Cancer Research in Frederick, Maryland, the research team found that the effectiveness of tamoxifen in cell cultures and in mice can be fully restored by the use of a compound called disulfide benzamide, or DIBA.
The investigators found that using the compound in mice engineered to have tamoxifen-resistant tumours led to a reduction in tumour growth of nearly 50 per cent when DIBA was administered together with tamoxifen.
Tamoxifen works by preventing the female hormone oestrogen, which fuels some breast cancers, from stimulating cancer cells via a molecule on their surface called the oestrogen receptor.
With continued tamoxifen treatment, the oestrogen receptors in the breast develop so that in some cases they can once again respond to oestrogen. DIBA seems to be able to reverse this development.
"This basic study generated exciting results in our mouse model and suggests a promising approach that might be tried in human patients," said Dr William Farrar of the NCI.
The study was conducted collaboratively between Georgetown University, the Baylor College of Medicine, the Methodist Hospital in Houston, and the National Institute of Allergy and Infectious Diseases.
It is published in the journal Cancer Cell.