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Gene sleuths search for clues to tamoxifen resistance


For many women with breast cancer, tamoxifen, a drug that inhibits the hormone estrogen, can be a lifesaver.  

The medicine has been used for decades to fight breast cancers that need estrogen to grow--about 75% of all breast cancers. Unfortunately, breast cancer cells can sometimes become resistant to tamoxifen, a dismal development for patients.

How do the cancer cells do it? Sherene Loi of the Peter MacCallum Cancer Centre in Australia is looking for the genes that underlie tamoxifen resistance.

Loi’s group used a recently developed technique called Gene Set Enrichment Analysis (GSEA) to screen 246 different estrogen-triggered breast cancer tissues, 147 of which were tamoxifen susceptible and the remaining 99 tamoxifen resistant.  

GSEA acts like a librarian, cataloging genes into related groups or gene sets, allowing researchers to go straight to the DNA shelf of interest as opposed to thumbing through a jumbled pile of genetic data.

The group reported in the journal BMC Medical Genomics on their findings: 78 sets of related genes that act differently in tamoxifen-resistant tumors compared with those susceptible to the drug.

The next steps would be to determine the genes’ precise contributions to tamoxifen resistance. That knowledge could help researchers eventually develop new drugs to counteract resistance or even replace tamoxifen altogether.

Image of mammogram revealing a tumor courtesy of DoctorKan via iStockphoto



The views expressed are those of the author and are not necessarily those of Scientific American.

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