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At the time of diagnosis, the majority of breast cancers are categorized as estrogen-receptor positive, or hormonesensitive, which means their cancerous cells may need estrogen togrow. Patients with this type of cancer often respond favorably to treatments called aromatase inhibitors,like tamoxifen, which cause cell death by preventing estrogen fromreaching the cancerous cells. Over time, however, the disease oftenbecomes resistant to estrogen deprivation from the drugs - makingtreatment options more limited. New findings that were presented at the AACR Annual Meeting 2012 byresearchers from Fox Chase Cancer Center in Philadelphia, identifya pair of proteins that could play a crucial role in restoringtreatment sensitivity to these resistant cancerous cells - possiblyleading to more treatment options in the future. In experiments on cancer cell lines, Joan Lewis-Wambi, Ph.D., atumor biologist at Fox Chase and lead author on the study, foundthat the two proteins, called STAT-1 and PLSCR-1, were 10 and 20times more abundant respectively in breast cancer cells that areresistant to estrogen deprivation than in cancerous cells that diedwithout estrogen. The researchers also showed that thetreatment-resistant cancerous cells underwent apoptosis, or celldeath, in the presence of estrogen - which suggests the hormone hasa complicated relationship with breast cancer. "Breast cancer cells that are hormone dependent need estrogen togrow," says Lewis-Wambi. "But these resistant cells have theopposite response to estrogen - instead of stimulating growth,estrogen actually induces death." Lewis-Wambi says she and her colleagues are trying to understandthe complex relationship between estrogen and the behavior of thesecancerous cells. In further experiments, they found increasedlevels of the two proteins when estrogen caused apoptosis in thecancerous cells. Previous experiments have shown that the proteinsare also associated with inteferon-alpha, a protein that promotescell death and is often used to treat solid tumors. The new findings suggest that a therapy that uses estrogen, alongwith interferon-alpha, may offer a treatment option for patientswhose disease is resistant to estrogen-depriving drugs. Such atreatment may use the two proteins to successfully induce thecancerous cells to undergo cell death. "The models we've developed in the lab are reflective of whathappens in the clinic when you have patients with hormone-dependentdisease," says Lewis-Wambi. "Initially they respond to treatment,but over time the disease becomes resistant to the drug, and thedrug no longer works." Previous studies have suggested that the STAT-1 and PLSCR-1proteins help induce cell death, but their exact functions haveremained a mystery. Lewis-Wambi and her colleagues, includingresearchers from the University of Rochester, suspected that theproteins might help explain how interferon-alpha works in a cell.The researchers studied the proteins using cancer cells that wereoriginally estrogen-receptor positive but, over time, developedresistance to drugs that starved them of estrogen. Lewis-Wambi says that they're now following up their promising invitro results with in vivo experiments to see if the proteinsbehave similarly in animal models. Once they can demonstrate theresults in animals, the scientists can think about how their workmight influence treatment. In addition to suggesting an interferon- and estrogen-basedtreatment, the proteins may help identify patients most likely torespond to a particular kind of therapy. This kind of personalizedcancer treatment, based on the molecular biology of a person'sdisease rather than the site or size of the tumor, has thepotential to be more effective and have fewer side effects thanconventional chemotherapies. "We know that no two patients are the same," Lewis-Wambi says. "Onedrug may work perfectly well in one patient but have no effect inanother. That comes back to the fact that a tumor's molecularprofile looks different from one individual to another. Our goal isto identify the genes that make patients more or less likely torespond to a drug. Then you're treating the individual, as opposedto the group." Additional References Citations. We are high quality suppliers, our products such as Pesticide Formulations Manufacturer , Grass Herbicide for oversee buyer. To know more, please visits Pesticide Technical.
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