Featured Research

from universities, journals, and other organizations

Possible therapy for tamoxifen resistant breast cancer identified

Date:
August 30, 2012
Source:
Ohio State University Medical Center
Summary:
A study has discovered how tamoxifen-resistant breast-cancer grows and proliferates. It also identifies an experimental agent that might offer a novel targeted therapy for tamoxifen-resistant breast cancer.

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," she says. "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.

Funding from the NIH/National Cancer Institute (grants CA137567 and CA133250) and a Pelotonia Idea grant supported this research.

Other Ohio State researchers involved in this study were Yuanzhi Lu, Kun-yu Teng, Gerard Nuovo, Xiaobai Li and Charles L. Shapiro.


Story Source:

The above story is based on materials provided by Ohio State University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. Ramaswamy, Y. Lu, K.-y. Teng, G. Nuovo, X. Li, C. L. Shapiro, S. Majumder. Hedgehog signaling is a novel therapeutic target in tamoxifen resistant breast cancer aberrantly activated by PI3K/AKT pathway. Cancer Research, 2012; DOI: 10.1158/0008-5472.CAN-12-1248

Cite This Page:

Ohio State University Medical Center. "Possible therapy for tamoxifen resistant breast cancer identified." ScienceDaily. ScienceDaily, 30 August 2012. <www.sciencedaily.com/releases/2012/08/120830105427.htm>.
Ohio State University Medical Center. (2012, August 30). Possible therapy for tamoxifen resistant breast cancer identified. ScienceDaily. Retrieved August 23, 2014 from www.sciencedaily.com/releases/2012/08/120830105427.htm
Ohio State University Medical Center. "Possible therapy for tamoxifen resistant breast cancer identified." ScienceDaily. www.sciencedaily.com/releases/2012/08/120830105427.htm (accessed August 23, 2014).

Share This




More Health & Medicine News

Saturday, August 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins