Featured Research

from universities, journals, and other organizations

Inflammatory pathway spurs cancer stem cells to resist HER2-targeted breast cancer treatment

Date:
July 19, 2012
Source:
University of Michigan Health System
Summary:
Researchers have discovered one reason why the cancer cells become resistant to Herceptin: They turn on a completely different pathway, one that is involved in inflammation, fueling the cancer independently of HER2.

Breast cancer treatments such as Herceptin that target a marker called HER2 have dramatically improved outcomes for women with this type of cancer. But nearly half of these cancers are resistant to Herceptin from the start and almost all of them will eventually become resistant.

Now, researchers at the University of Michigan Comprehensive Cancer Center have discovered one reason why the cancer cells become resistant: They turn on a completely different pathway, one that is involved in inflammation, fueling the cancer independently of HER2.

The pathway at work involves a protein called Interleukin-6, or IL-6. The researchers also showed in mice that a drug that blocks IL-6 can stop this effect and overcome the Herceptin resistance.

"Resistance to HER2-targeted therapies remains a major challenge in treating breast cancer. Our study suggests that an IL-6 inhibitor in combination with Herceptin may be a valuable addition for treating HER2-positive breast cancer," says senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

Results of the study will be published in the Aug. 24 issue of Molecular Cell.

Not only are these cells resistant to Herceptin, but they develop higher proportions of cancer stem cells, the small number of cells within a tumor that fuel the growth and spread. This makes the tumor extremely aggressive and likely to spread throughout the body. The IL-6 inhibitor also was shown to prevent this increase in cancer stem cells.

"There is evidence that patients with a lot of IL-6 tend to do poorly. What we found now is that in many of the Herceptin-resistant breast cancers, the IL-6 inflammation loop is driving the cancer stem cell," says lead study author Hasan Korkaya, D.V.M., Ph.D., research assistant professor of internal medicine at the U-M Medical School.

The researchers found that blocking the IL-6 inflammatory loop almost completely blocked the cancer and the stem cells. Mice treated with the IL-6 blocker along with Herceptin immediately after the cancer developed never became resistant to Herceptin.

IL-6 is known to play a role in inflammatory diseases such as rheumatoid arthritis, as well as obesity and cancer. Tocilizumab, a drug that targets this protein, is approved by the U.S. Food and Drug Administration to treat rheumatoid arthritis.

The researchers are developing a clinical trial to test the IL-6 blocker along with Herceptin. That trial will likely open early in 2013.

Breast cancer statistics: 229,060 Americans will be diagnosed with breast cancer this year and 39,920 will die from the disease, according to the American Cancer Society

Additional authors: Gwang-il Kim, April Davis, Fayaz Malik, N. Lynn Henry, Suthinee Ithimakin, Ahmed A. Quraishi, Nader Tawakkol, Rosemarie D'Angelo, Amanda Paulson, Susan Chung, Tahra Luther, Hayley S. Paholak, Suling Liu, Khaled Hassan, Qin Zen, Shawn G. Clouthier

Funding: National Institutes of Health grants CA 129765 and CA 101860, Susan G. Komen for the Cure


Story Source:

The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hasan Korkaya, Gwang-il Kim, April Davis, Fayaz Malik, N.Lynn Henry, Suthinee Ithimakin, AhmedA. Quraishi, Nader Tawakkol, Rosemarie D'Angelo, Amanda K. Paulson, Susan Chung, Tahra Luther, HayleyJ. Paholak, Suling Liu, Khaled A. Hassan, Qin Zen, ShawnG. Clouthier, MaxS. Wicha. Activation of an IL6 Inflammatory Loop Mediates Trastuzumab Resistance in HER2 Breast Cancer by Expanding the Cancer Stem Cell Population. Molecular Cell, 2012; DOI: 10.1016/j.molcel.2012.06.014

Cite This Page:

University of Michigan Health System. "Inflammatory pathway spurs cancer stem cells to resist HER2-targeted breast cancer treatment." ScienceDaily. ScienceDaily, 19 July 2012. <www.sciencedaily.com/releases/2012/07/120719132602.htm>.
University of Michigan Health System. (2012, July 19). Inflammatory pathway spurs cancer stem cells to resist HER2-targeted breast cancer treatment. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2012/07/120719132602.htm
University of Michigan Health System. "Inflammatory pathway spurs cancer stem cells to resist HER2-targeted breast cancer treatment." ScienceDaily. www.sciencedaily.com/releases/2012/07/120719132602.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
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