With the advent of the cold season, several of my classes here at UT Austin have been plagued with the echoes of people coughing; the sounds often drown the professor’s voice!  I have also started to feel under the weather as of a few days ago.  To make matters worse, I seem to have acquired resistance over the years to the most cold medications.

The problem of drug resistance is not only for common in illnesses such as the cold or bacterial infections, but also in much more severe conditions such as breast cancer.  Luckily, researchers at Georgetown Lombardi Comprehensive Cancer Center have found a natural additive for Tamoxifen (the most common treatment for breast cancer) that will prevent patients from developing resistance against it.

Tamoxifen is the most prevalent prescription for estrogen positive breast cancers. The presence of estrogen perpetuates cancer in these cases; tamoxifen blocks estrogen receptors on cell surfaces.  When estrogen doesn’t bind to the cancer cell, it is accepted as a signal for apoptosis (cell death).  The cell death signal activates the protein CASP8, which in turn activates another protein, Bcl2.  These two proteins activate programmed cell death and eliminate cancer cells.  The problem is that the protein complex nuclear factor kappa B (NF-kB) can also be activated when estrogen is not present and NF-kB turns off both CASP8 and Bcl2. So even though Tamoxifen works and prevents the cellular binding of estrogen, NF-kB overrides the apoptosis mechanism and allows the cancer cells to stay alive. People who have developed resistance to Tamoxifen have been found to over-express NF-kB.

The study found that Parthenolide, a derivative of the feverfew plant, successfully blocks NF-kB so that cells are re-sensitized to Tamoxifen.  Researchers are optimistic, but stress that the results are preliminary.  Targeting the survival mechanism of any cell can be a tricky task to handle considering that just one wrong target could potentially harm many healthy cells.   However, as more details on the mechanism are discovered, researchers are hopeful that Parthenolide can be used to combat the growing problem of drug-resistance in breast cancers.

Discussion Question: Why would an estrogen positive breast cancer cell be programmed to survive even though it will not receive any more estrogen?

News Article: http://www.sciencedaily.com/releases/2010/02
Paper Abstract: http://www.fasebj.org/cgi/content/abstract/fj.09-138305v1