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on -- the target of the drug, evade therapy, and then re-acquire the oncogene to promote tumor growth when the drug is withdrawn."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 July 31, 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 July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 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