Riddle of Anti-Estrogen Resistance May Be Solved
September 27, 2011 – Resistance to anti-estrogenic agents used to treat breast cancer appears to be due to a natural stress response in cells, according to researchers at Georgetown Lombardi Comprehensive Cancer Center.
The researchers believe this may lead to a new drug target – the biochemical molecules involved in the response.
Hijacking and Switching
Most breast cancers are fueled by estrogen, and anti-estrogenic agents often work for a time to control the cancers. But the cancer treatment often stops working, leaving patients with limited options.
Lombardi, part of the Georgetown University Medical Center (GUMC), reported its findings at the American Association for Cancer Research’s 2011 annual meeting.
The researchers found that breast cancer cells protect themselves against two anti-estrogen drugs – Tamoxifen and Faslodex – by hijacking and switching on a biological process inside the cells normally used when wrongly shaped proteins are produced.
Before this study, it wasn’t known that stress response could be triggered when breast cancer cells are “attacked” by anti-estrogen drugs, says the study’s lead investigator, Ayesha Shajahan.
Shajahan is an oncology research instructor and researcher in the laboratory of Robert Clarke, GUMC dean for research and professor of oncology.
If a response is activated, cells can do one of two things, Shajahan says. They can turn on a “pro-survival pathway” or they can turn on a process that ultimately destroys the cells.
The cells the researchers studied all chose the survival mode, which allows the cells to resist anti-cancer treatment.
“We found that anti-estrogen resistant cancer cells are much more likely to turn on the pro-survival pathway than are cells that are sensitive to estrogen,” Shajahan says.