New strategy to overcome drug resistance (tamoxifen) in breast cancer ?

A solution to tamoxifen resistance is sorely needed, and if a strategy like this can work, it would make a difference in our clinical care of breast cancer,” says the study’s lead investigator. Yes, the researchers lead by Dr. Robert Clarke of Georgetown Lombardi Comprehensive Cancer Center have come with an interesting finding i.e., combining tamoxifen, the world’s most prescribed breast cancer agent  with a compound (Parthenolide,  see left structure source : ChemSpider) found in the flowering plant feverfew (right picture) may prevent initial or future resistance to the drug. 

 

As per the claim by the researchers tamoxifen resistance is regulated by the protein complex NF- κB (nuclear factor kappa B), which is often found to be over-expressed in ER+ breast cancer. NF- κB is known to help cells survive when damaged. Earlier the same researchers have also found that, the resistance to another tamoxifen-like drug, fulvestrant, was controlled by a protein (Bcl2) which is also regulated by NF- κB. These findings  encouraged  them to think that,  blocking NF- κB might affect tamoxifen resistance. 

Researchers conducted a variety of tests using parthenolide, which has been shown to act on NF- κB. They found that in resistant breast cancer cells, the chemical blocked the activity of NF- κB, making the cells sensitive once again to tamoxifen. Researchers then silenced NF- κB in tamoxifen resistant cells, and found that this had the same effect as using parthenolide. 

They further found that increased activation of NF- κB can alter sensitivity of tamoxifen by modulating the protein CASP8 (which is involved in programmed cell death), which affects Bcl2  and there by  helping  to  push a damaged cell to die.  
 

About Feverfew : 

Feverfew (Tanacetum parthenium) is edible and medicinal plant and   has a good reputation as alternative medicine and extensive research has proved it to be of special benefit in the treatment of certain types of migraine headaches and rheumatism or arthritis. The plant is rich in sesquiterpene lactones, the principal one being parthenolide. Parthenolide helps prevent excessive clumping of platelets and inhibits the release of certain chemicals, including serotonin and some inflammatory mediators. (other constituents are: pinene, pinene derivatives, bornylacetate, angelate, b-farnesine, spiroketalenol ethers, flavonoid glycosides and costic acid) .

Though the leaves and flowering heads are reported to possess antiinflammatory, antispasmodic, aperient,  sedative, stimulant, stomachic, vasodilator and vermifuge. activities, this type of activity has been reported  for the first time. 

 

Researchers conclude that the chemical, clearly has the potential to be able to figure out fairly  and it can help solve tamoxifen’s resistance problem with a caution that the science is much too early to make any recommendations. Let us wait for some more time.......

Ref :  Robert Clarke et. al., Feb. 12 in FASEB