Featured Research

from universities, journals, and other organizations

HIV and breast cancer may share a common enemy: Nelfinavir

Date:
October 11, 2012
Source:
Johns Hopkins Medicine
Summary:
After screening more than 2,300 drugs for their ability to halt the growth of breast cancer cells, researchers have discovered that the anti-HIV drug nelfinavir slows the progress of HER2-positive tumor cells, even if they are resistant to other breast cancer drugs.

After screening more than 2,300 drugs for their ability to halt the growth of breast cancer cells, Johns Hopkins researchers have discovered that the anti-HIV drug nelfinavir slows the progress of HER2-positive tumor cells, even if they are resistant to other breast cancer drugs.

In a report on the discovery published online Oct. 5 in the Journal of the National Cancer Institute, the investigators also say nelfinavir worked at concentrations already approved by the U.S. Food and Drug Administration. So-called HER2-positive breast cancers, which contain the protein HER2 and comprise 25 to 30 percent of cases, are more aggressive and less responsive to hormone treatments than HER2-negative cancers, a status that has fueled the search for better drug therapies and especially for ways to speed up the search by "repurposing" drugs already on the market.

"New drug development, beginning from scratch, is extremely expensive and time-consuming, taking an estimated $1 billion and more than 10 years to get each new compound to market," says Jun O. Liu, Ph.D., professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine. "An existing drug has already passed most of the costly safety and regulatory hurdles," says Liu, who has worked on "repurposing" them for almost a decade.

To speed up drug discovery, Liu and his colleagues created the Johns Hopkins Drug Library, which currently includes nearly 2,900 drugs, most of which are FDA-approved. All have passed through phase I clinical trials to test their dosing safety.

In the new study, Liu and his team began with breast cancer cells from two patients, then tested all of the drugs in the library for their ability to stop cells from multiplying. Seventy of the best performers were selected for round two, in which they tested cells from seven patients, each genetically different, to see which drugs worked best.

Five of these drugs were selected for their ability to stop or slow the growth of HER2-positive cells. One of the five, nelfinavir, was selected for further testing because it appeared to work better than the others on HER2-positive cells and, says Liu, seemed to interfere with the protein HER2 itself. Nelfinavir was also already known to have a broad anti-cancer effect against melanoma, non-small-cell lung cancer and pancreatic cancer.

To see if nelfinavir worked in mice implanted with HER2-positive or HER2-negative human breast cancer cells, the team gave mice a fake drug or a human-dose equivalent of nelfinavir, then measured tumor size for a month. Nelfinavir slowed the growth of HER2-positive tumors, but had no effect on HER2-negative tumors in mice.

To see if nelfinavir could slow the growth of tumors that had become resistant to the commonly used breast cancer drugs trastuzumab and lapatinib, the researchers treated drug-resistant and non-drug-resistant cells growing in the lab with nelfinavir, trastuzumab or lapatinib. Only nelfinavir was able to prevent both drug-resistant and non-drug-resistant cells from growing.

When combating HIV, nelfinavir inhibits enzymes called proteases that break down proteins, and Liu's team wanted to know if nelfinavir uses that same mechanism to slow the growth of breast cancer cells. To test this, they gave nelfinavir to a wide variety of yeast cells, which are commonly used to study drug effects on genes because of the similarity between their cells and ours. Each type of yeast was genetically engineered to make less of a particular protein, making them more vulnerable to environmental stresses. They found that when yeast making less of the HSP90 protein were given the drug, the cells died, suggesting that nelfinavir interacts with HSP90, which is not a protease.

"This was interesting because we know that HSP90 also binds to HER2, and we now think that nelfinavir may be interfering with this interaction," says Liu. "This is a good starting point for clinical trials," he adds.

Other authors of the paper include Joong Sup Shim, Rajini Rao and Inkyu Han from The Johns Hopkins University; Kristin Beebe and Len Neckers from the National Cancer Institute; and Rita Nahta from Emory University School of Medicine.

This work was supported by grants from the National Cancer Institute (R01CA122814), the National Center for Research Resources (UL1 RR025005), Flight Attendant Medical Research Institute, the Commonwealth Foundation and the National Institute of Allergy and Infectious Diseases (R01AI065983).


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. S. Shim, R. Rao, K. Beebe, L. Neckers, I. Han, R. Nahta, J. O. Liu. Selective Inhibition of HER2-Positive Breast Cancer Cells by the HIV Protease Inhibitor Nelfinavir. JNCI Journal of the National Cancer Institute, 2012; DOI: 10.1093/jnci/djs396

Cite This Page:

Johns Hopkins Medicine. "HIV and breast cancer may share a common enemy: Nelfinavir." ScienceDaily. ScienceDaily, 11 October 2012. <www.sciencedaily.com/releases/2012/10/121011123713.htm>.
Johns Hopkins Medicine. (2012, October 11). HIV and breast cancer may share a common enemy: Nelfinavir. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2012/10/121011123713.htm
Johns Hopkins Medicine. "HIV and breast cancer may share a common enemy: Nelfinavir." ScienceDaily. www.sciencedaily.com/releases/2012/10/121011123713.htm (accessed April 19, 2014).

Share This



More Health & Medicine News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
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:

More Coverage


HIV Drug Shows Efficacy in Treating Mouse Models of HER2+ Breast Cancer, Study Suggests

Oct. 5, 2012 The HIV protease inhibitor, Nelfinavir, can be used to treat HER2-positive breast cancer in the same capacity and dosage regimen that it is used to treat HIV, according to a new ... read more
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