Featured Research

from universities, journals, and other organizations

New agent might control breast-cancer growth and spread

Date:
April 22, 2013
Source:
Ohio State University Medical Center
Summary:
A new study suggests that an unusual experimental drug can reduce breast-cancer aggressiveness, reverse resistance to the drug fulvestrant and perhaps improve the effectiveness of other breast-cancer drugs. The findings suggest a new strategy for treating breast cancer.

The drug AS1411 works by blocking the cell's production of regulatory molecules called microRNA, some types of which are associated with cancer. Specifically, the drug inhibits a protein called nucleolin that plays a critical role in the microRNA maturation process. Left: Steps in the microRNA maturation process. Right: How AS1411 interferes with microRNA maturation.
Credit: The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute

A new study led by researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) suggests that an unusual experimental drug can reduce breast-cancer aggressiveness, reverse resistance to the drug fulvestrant and perhaps improve the effectiveness of other breast-cancer drugs.

The findings of the laboratory and animal study, published in the Journal of Experimental Medicine, suggest a new strategy for treating breast cancer, the researchers say.

The drug, called AS1411, belongs to a class of agents called G-rich aptamers. The agent works by blocking the cell's production of molecules called microRNA, some types of which are associated with cancer. Specifically, the drug inhibits a protein called nucleolin that plays a critical role in the microRNA maturation process.

MicroRNA molecules help cells control the amount and kinds of proteins they make, and abnormal levels of certain microRNAs are a hallmark of many cancers.

"This study of the role of nucleolin in micro RNA regulation has clear clinical implications," says principal investigator Dr. Carlo M. Croce, director of Ohio State's Human Cancer Genetics program and a member of the OSUCCC -- James Molecular Biology and Cancer Genetics program.

"It supports a novel treatment for breast cancer that reduces cancer aggressiveness and restores drug-sensitivity by inhibiting the processing of specific microRNAs that are highly expressed in cancers."

First author Flavia Pichiorri, assistant professor of hematology, notes that nucleolin is a promising therapeutic target for microRNA modulation in cancer cells.

"To our knowledge, this is the first large study to show a clear association between nucleolin and specific microRNAs that are causally involved in cancer," she says. "We also believe it is the first study to show that targeting nucleolin with a G-rich aptamer can control breast-cancer metastasis in an animal model through microRNA regulation."

The study's key technical findings include:

  • Nucleolin is present at abnormally high levels in breast cancer cells.
  • AS1411 reduces nucleolin levels and inhibits the processing of certain cancer-associated microRNAs, including miR-21, miR-103, miR-221 and miR-222, whose overexpression in breast cancer is associated with drug resistance and aggressiveness.
  • AS1411 affects breast-cancer-cell motility and invasiveness by reducing the expression of several genes targeted by nucleolin-related microRNAs (e.g., PTEN);
  • Impairing nucleolin in fulvestrant-resistant breast-cancer cells restores sensitivity to the drug, suggesting that agents targeting nucleolin can improve the effectiveness of conventional anti-cancer agents.

Funding from the NIH/National Cancer Institute (grants CA154200 and CA107106), the Kimmel Foundation and the Spielman Fund for Breast Cancer Research supported this research.


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. Flavia Pichiorri, Dario Palmieri, Luciana De Luca, Jessica Consiglio, Jia You, Alberto Rocci, Tiffany Talabere, Claudia Piovan, Alessandro Lagana, Luciano Cascione, Jingwen Guan, Pierluigi Gasparini, Veronica Balatti, Gerard Nuovo, Vincenzo Coppola, Craig C. Hofmeister, Guido Marcucci, John C. Byrd, Stefano Volinia, Charles L. Shapiro, Michael A. Freitas, and Carlo M. Croce. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation. Journal of Experimental Medicine, 2013 DOI: 10.1084/jem.20120950

Cite This Page:

Ohio State University Medical Center. "New agent might control breast-cancer growth and spread." ScienceDaily. ScienceDaily, 22 April 2013. <www.sciencedaily.com/releases/2013/04/130422101137.htm>.
Ohio State University Medical Center. (2013, April 22). New agent might control breast-cancer growth and spread. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2013/04/130422101137.htm
Ohio State University Medical Center. "New agent might control breast-cancer growth and spread." ScienceDaily. www.sciencedaily.com/releases/2013/04/130422101137.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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