Featured Research

from universities, journals, and other organizations

Brain cancer cells hide while drugs seek

Date:
December 5, 2013
Source:
University of California, San Diego Health Sciences
Summary:
A team of scientists has found that brain cancer cells resist therapy by dialing down the gene mutation targeted by drugs, then re-amplify that growth-promoting mutation after therapy has stopped.

Human brain specimen with glioblastoma multiforme.
Credit: University of California, San Diego School of Medicine

A team of scientists, led by principal investigator Paul S. Mischel, MD, a member of the Ludwig Institute for Cancer Research and professor in the Department of Pathology at the University of California, San Diego School of Medicine, has found that brain cancer cells resist therapy by dialing down the gene mutation targeted by drugs, then re-amplify that growth-promoting mutation after therapy has stopped.

The findings are published in the December 5, 2013 online issue of Science.

"This discovery has considerable clinical implications because if cancer cells can evade therapy by a 'hide-and-seek' mechanism, then the current focus (of drug therapies) is unlikely to translate into better outcomes for patients," said Mischel.

In recent years, new cancer therapies have emerged that target tell-tale gene mutations to identify specific cancer cells for destruction. Unfortunately, a variety of "resistance mechanisms" have also emerged, among them incomplete target suppression, second-site mutations and activation of alternative kinases or enzymes that maintain growth-promoting signals to the cancer itself.

"Most research is aimed at developing better drugs or better drug combinations to suppress these downstream signals," Mischel said. "However, one thing that has not been carefully considered is whether cancer cells can modulate the levels of -- and thus their dependence on -- the target of the drug, evade therapy, and then re-acquire the oncogene to promote tumor growth when the drug is withdrawn."

Mischel and colleagues, including Webster K. Cavenee, PhD, and Frank B. Furnari, PhD, of the Ludwig Institute and the UC San Diego School of Medicine, investigated the behavior of glioblastoma multiforme (GBM), the most common malignant primary brain cancer in adults. More than 9,000 new cases of the disease are diagnosed each year in the United States and effective treatments are limited. The tumors are aggressive and resistant to current therapies, such as surgery, radiation and chemotherapy. The median survival rate for newly diagnosed GBM patients is just 14 months.

GBM is characterized by a mutated variant of the epidermal growth factor receptor known as EGFRvIII that is found on extrachromosomal DNA in cancer cells. EGFRvIII promotes tumor growth. Some new drugs kill cancer cells by specifically suppressing or inhibiting EGFRvIII, but lose effectiveness as drug resistance soon develops.

The researchers found that this resistance may be due to the cancer cells temporarily dumping their extrachromosomal EGFRvIII, which essentially renders them invisible to drugs looking for that particular mutation. When the drug therapy is halted, the EGFRvIII reappears at previous levels and accelerated tumor growth resumes.

"This is, to the best of our knowledge, the first demonstration that reversible loss of an oncogene on extrachromosomal DNA can lead to targeted cancer drug resistance," said Mischel, who hoped the findings would "shift the discussion about what directions need to be taken to improve the success rate for targeted cancer treatments."


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. A. Nathanson, B. Gini, J. Mottahedeh, K. Visnyei, T. Koga, G. Gomez, A. Eskin, K. Hwang, J. Wang, K. Masui, A. Paucar, H. Yang, M. Ohashi, S. Zhu, J. Wykosky, R. Reed, S. F. Nelson, T. F. Cloughesy, C. D. James, P. N. Rao, H. I. Kornblum, J. R. Heath, W. K. Cavenee, F. B. Furnari, P. S. Mischel. Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA. Science, 2013; DOI: 10.1126/science.1241328

Cite This Page:

University of California, San Diego Health Sciences. "Brain cancer cells hide while drugs seek." ScienceDaily. ScienceDaily, 5 December 2013. <www.sciencedaily.com/releases/2013/12/131205141307.htm>.
University of California, San Diego Health Sciences. (2013, December 5). Brain cancer cells hide while drugs seek. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2013/12/131205141307.htm
University of California, San Diego Health Sciences. "Brain cancer cells hide while drugs seek." ScienceDaily. www.sciencedaily.com/releases/2013/12/131205141307.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:
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