Featured Research

from universities, journals, and other organizations

Weakness exposed in most common cancer gene

Date:
February 10, 2014
Source:
NYU Langone Medical Center
Summary:
Researchers have found a biological weakness in the workings of the most commonly mutated gene involved in human cancers, known as mutant K-Ras, which they say can be exploited by drug chemotherapies to thwart tumor growth.

NYU Langone Medical Center researchers have found a biological weakness in the workings of the most commonly mutated gene involved in human cancers, known as mutant K-Ras, which they say can be exploited by drug chemotherapies to thwart tumor growth.

Mutant K-Ras has long been suspected of being the driving force behind more than a third of all cancers, including colon, lung, and a majority of pancreatic cancers. Indeed, Ras cancers, which are unusually aggressive, are thought of as "undruggable" because every previous attempt to stall their growth has failed.

Reporting in the journal Cancer Cell online Feb. 10, researchers in the lab of NYU Langone's Dafna Bar-Sagi, PhD, led by Elda Grabocka, PhD, showed in experiments in human cancer cells that K-Ras tumor growth was highly dependent on the cells' constant need to check and mend their DNA.

Cell DNA is routinely damaged by several factors, including stress or ultraviolet light radiation, and must be repaired in order for cells to grow by cell division. In cancer cells, such "wear and tear" is accelerated.

In the study, researchers discovered how a commonly used chemotherapy drug could be much more effective in killing K-Ras cancer cells when their ability to check their DNA for any damage was blocked, by cutting off the activity of two related genes, H-Ras and N-Ras.

"Our finding suggests that K-Ras cancers can be made more susceptible to existing therapies by interfering with their DNA repair mechanisms," says Dr. Bar-Sagi, senior study investigator and biochemist. "What some researchers have described as therapeutic 'mission impossible' may now become a 'mission doable'," adds Dr. Bar-Sagi, senior vice president and vice dean for science, and chief scientific officer of NYU Langone Medical Center.

Lead study investigator and cancer biologist Dr. Grabocka, a postdoctoral fellow at NYU Langone, says the latest findings are believed to be the first to show that Ras mutations are part of a network of different forms of Ras acting in concert to determine how cancer cells respond to drug chemotherapies.

The team's investigation began with experiments to unravel how Ras signaling leads to the uncontrolled growth of cancer cells. They found that blocking the production of H-Ras and N-Ras in mutant K-Ras cells caused the buildup of damaged DNA and slowed down cell growth.

Specifically, Grabocka points out, the team found that K-Ras cancer cells, in the absence of H-Ras and N-Ras, failed to stop and repair their DNA at a key phase in cell division, controlled by an enzyme called checkpoint kinase 1, or Chk1.

Using K-Ras cancer cells developed at NYU Langone, Bar-Sagi and her team then set out to test the effects of the chemotherapy drug irinotecan on tumor growth.

Only when the drug was delivered in combination with the inactivation of H-Ras and N-Ras did tumor shrinkage and cell death occur.

"Discovering more about how these different forms of Ras act on one another -- including how they control DNA damage repair at Chk1 in combination with chemotherapy -- could help us design drugs that greatly stall disease progression," says Dr. Grabocka.

Researchers plan further experiments on the biological interdependency of Ras proteins and what other chemotherapies might be involved in slowing cancer growth. Their goal, Dr. Grabocka says, is to "map out" the Ras signaling pathways and to identify as many therapeutic drug targets as possible. "Our research is focused on finding multiple targets in K-Ras cancers, all working against what is known as its 'tumor fitness,' and weakening it so that it is as vulnerable as possible to chemotherapy," says Dr. Grabocka.


Story Source:

The above story is based on materials provided by NYU Langone Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Elda Grabocka, Yuliya Pylayeva-Gupta, MathewJ.K. Jones, Veronica Lubkov, Eyoel Yemanaberhan, Laura Taylor, HaoHsuan Jeng, Dafna Bar-Sagi. Wild-Type H- and N-Ras Promote Mutant K-Ras-Driven Tumorigenesis by Modulating the DNA Damage Response. Cancer Cell, 2014; 25 (2): 243 DOI: 10.1016/j.ccr.2014.01.005

Cite This Page:

NYU Langone Medical Center. "Weakness exposed in most common cancer gene." ScienceDaily. ScienceDaily, 10 February 2014. <www.sciencedaily.com/releases/2014/02/140210135828.htm>.
NYU Langone Medical Center. (2014, February 10). Weakness exposed in most common cancer gene. ScienceDaily. Retrieved September 3, 2014 from www.sciencedaily.com/releases/2014/02/140210135828.htm
NYU Langone Medical Center. "Weakness exposed in most common cancer gene." ScienceDaily. www.sciencedaily.com/releases/2014/02/140210135828.htm (accessed September 3, 2014).

Share This



More Health & Medicine News

Wednesday, September 3, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Snack Attack: Study Says Action Movies Make You Snack More

Snack Attack: Study Says Action Movies Make You Snack More

Newsy (Sep. 2, 2014) You're more likely to gain weight while watching action flicks than you are watching other types of programming, says a new study published in JAMA. Video provided by Newsy
Powered by NewsLook.com
U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Doctors Fear They're Losing Battle Against Ebola

Doctors Fear They're Losing Battle Against Ebola

AP (Sep. 2, 2014) As a third American missionary is confirmed to have contracted Ebola in Liberia, doctors on the ground in West Africa fear they're losing the battle against the outbreak. (Sept. 2) Video provided by AP
Powered by NewsLook.com
Tech Giants Bet on 3D Headsets for Gaming, Healthcare

Tech Giants Bet on 3D Headsets for Gaming, Healthcare

AFP (Sep. 2, 2014) When Facebook acquired the virtual reality hardware developer Oculus VR in March for $2 billion, CEO Mark Zuckerberg hailed the firm's technology as "a new communication platform." Duration: 02:24 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