Navigation Links
Possible therapy for tamoxifen resistant breast cancer identified
Date:8/30/2012

  • The hormone estrogen stimulates the growth of breast cancers that are estrogen-receptor positive, the most common form of breast cancer.
  • The drug tamoxifen blocks this estrogen effect and prolongs the lives of, and helps to cure, patients with estrogen-sensitive breast cancer.
  • About 30 percent of these patients have tumors that are resistant to tamoxifen.
  • This study shows how these resistant tumors survive and grow, and it identifies an experimental agent that targets these breast cancers.

  • COLUMBUS, Ohio A study by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James) has discovered how tamoxifen-resistant breast-cancer cells grow and proliferate. It also suggests that an experimental agent might offer a novel targeted therapy for tamoxifen-resistant breast cancer.

    Like a second door that opens after the first door closes, a signaling pathway called hedgehog (Hhg) can promote the growth of breast-cancer cells after tamoxifen shuts down the pathway activated by the hormone estrogen. A second signaling pathway, called PI3K/AKT, is also involved.

    Activation of the Hhg pathway renders tamoxifen treatment ineffective and enables the tumor to resume its growth and progression. As part of the study, the researchers analyzed over 300 human tumors and found that the tumors with an activated Hhg pathway had a worse prognosis.

    Finally, the researchers showed that an experimental drug called vismodegib, which blocks the Hhg pathway, inhibits the growth of tamoxifen-resistant human breast tumors in an animal model. The drug is in clinical trials testing for other types of cancer.

    Currently, chemotherapy is used to treat hormone-resistant breast cancers, but this is associated with significant side effects. This study has identified targeted therapies that could be an alternative to chemotherapy for these resistant tumors.

    The study is published in the journal Cancer Research.

    "Our findings suggest that we can target this pathway in patients with estrogen-receptor breast cancers who have failed tamoxifen therapy," says first author Dr. Bhuvaneswari Ramaswamy, a medical oncologist specializing in breast cancer at the OSUCCC James.

    "We describe a link between the hedgehog signaling pathway, which promotes tamoxifen resistance and the PI3K/AKT pathway," says principal investigator Sarmila Majumder, research assistant professor in molecular and cellular biochemistry at the OSUCCC James. "Targeting the hedgehog pathway alone or in combination with the PI3K/AKT pathway could be a novel therapeutic option for treating tamoxifen-resistant breast cancer."

    Ramaswamy, an assistant professor of internal medicine at Ohio State, emphasizes that novel options are needed for these patients.

    "A combined targeted therapy using both hedgehog and PI3K inhibitors could lead to a novel treatment for endocrine-resistant tumors in the future without use of chemotherapy," says Ramaswamy. "And these agents we have identified are all in clinical development for other kinds of cancer."

    Approximately 230,000 new cases of breast cancer are expected in the United States in 2012, and almost 40,000 Americans will die from the disease. More than two-thirds of breast cancer cases show high levels of the estrogen receptor (ER). Doctors use the drug tamoxifen to treat these ER-positive tumors, and Ramaswamy notes that the drug has improved the disease-free survival of people with ER-positive breast cancer by 50 percent.

    "But 30 to 40 percent of patients taking tamoxifen become resistant to it after about five years," she says. Currently, there are very limited options for these patients and most end up receiving chemotherapy.

    Key findings for this study include:

  • Tamoxifen-resistant breast cancer depends on the Hhg pathway for cell growth;
  • The PI3K/AKT pathway protects key Hhg signaling proteins from degradation, which promotes activation of the Hhg pathway.
  • Analysis of 315 invasive breast cancers showed that high levels of the protein GLI1, an important Hhg marker, was correlated with poorer disease-free survival and overall survival.
  • "Our next step is to organize a clinical trial to evaluate vismodegib in patients with tamoxifen-resistant breast cancer," Ramaswamy says.


    '/>"/>

    Contact: Darrell E. Ward
    Darrell.Ward@osumc.edu
    614-293-3737
    Ohio State University Medical Center
    Source:Eurekalert

    Related medicine news :

    1. Statin Use Tied to Possible Boost in Cataract Risk
    2. FDA Cites Possible Source of Cantaloupe-Salmonella Outbreak
    3. Why living in the moment is impossible
    4. Genomic study of rare childrens cancer yields possible prognostic tool
    5. Doctors often dont disclose all possible risks to patients before treatment
    6. Wayne State research team finds possible clue to progression of MS
    7. DNA damage in roofers due to PAH exposure - possible cancer link
    8. In utero exposure to diesel exhaust a possible risk factor for obesity
    9. Mild HIV type slows development of AIDS and makes new preventive treatments possible
    10. Mutation in gene IDH a possible target for AML treatment
    11. Loss of protein SPDEF allows prostate cancer cells to gain foothold at possible sites of metastasis
    Post Your Comments:
    *Name:
    *Comment:
    *Email:
    (Date:6/27/2016)... ... 27, 2016 , ... TherapySites, the leading website ... Tennessee Counseling Association. This new relationship allows TherapySites to continue to ... adding exclusive benefits and promotional offers. , "TCA is extremely excited about this ...
    (Date:6/27/2016)... ... , ... TopConsumerReviews.com recently awarded their highest five-star rating to Best Buy Eyeglasses, ... the United States and Canada wear eyeglasses. Once considered to be a purely functional ... a fashion statement. Even celebrities use glasses as a way of creating an iconic ...
    (Date:6/26/2016)... , ... June 26, 2016 , ... Pixel Film Studios ... X. , "Film editors can give their videos a whole new perspective by using ... - CEO of Pixel Film Studios. , ProSlice Levels contains over 30 Different ...
    (Date:6/26/2016)... ... June 26, 2016 , ... Many women are ... with endometriosis. These women need a treatment plan to not only alleviate symptoms ... can help for preservation of fertility and ultimately achieving a pregnancy. The specialists ...
    (Date:6/25/2016)... ... ... Bruton Memorial Library on June 21 due to a possible lice infestation, as reported by ... lice: the parasite’s ability to live away from a human host, and to infest common ... the event that lice have simply gotten out of control. , As lice are a ...
    Breaking Medicine News(10 mins):
    (Date:6/26/2016)... 26, 2016 One of Australia,s ... formation of a new biotechnology company, Noxopharm Limited [ABN 50 608 ... IPO and to list on the ASX. Noxopharm is ... to enter a Phase 1 clinical study later this year. ... one of the biggest problems facing cancer patients - the ability ...
    (Date:6/26/2016)... 2016 Jazz Pharmaceuticals plc (Nasdaq: ... Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended ("HSR"), ... Inc. ("Celator"; Nasdaq: CPXX ) expired effective ... As previously announced on May 31, 2016, ... agreement under which Jazz Pharmaceuticals has commenced a tender ...
    (Date:6/26/2016)... 27, 2016  VMS Rehab Systems, Inc. ( www.vmsrehabsystemsinc.com ... whatever measures required to build a strong and stable ... currently listed on the OTC Markets-pink current trading platform. ... CEO, "We are seeing an anomaly in market trading ... only by the Company, but shareholders and market players ...
    Breaking Medicine Technology: