Featured Research

from universities, journals, and other organizations

Novel approach scores first success against elusive cancer gene

Date:
September 10, 2011
Source:
Dana-Farber Cancer Institute
Summary:
Researchers successfully disrupted the function of the gene MYC by tampering with the gene's "on" switch and growth signals in multiple myeloma cells, offering promising strategy for treating myeloma and other cancers driven by the MYC gene.

Dana-Farber Cancer Institute scientists have successfully disrupted the function of a cancer gene involved in the formation of most human tumors by tampering with the gene's "on" switch and growth signals, rather than targeting the gene itself. The results, achieved in multiple myeloma cells, offer a promising strategy for treating not only myeloma but also many other cancer types driven by the gene MYC, the study authors say.

Related Articles


Their findings are being published by the journal Cell on its website Sept. 1 and in its Sept. 16 print edition.

"Cancer is a disease of disregulation of growth genes in a cell, and MYC is a master regulator of these genes," says James E. Bradner, MD, of Dana-Farber, one of the study's senior authors. Previous attempts to shut down MYC by inhibiting it directly with drug molecules have been notably unsuccessful. "In this study, our idea was to switch MYC off, interfering with its ability to activate the cell-growth program."

They did so with a small molecule called JQ1, developed by Dana-Farber's Jun Qi, PhD, a co-author of the new study and namesake of JQ1. In multiple myeloma, MYC is hyperactive -- constantly ordering cells to grow and divide -- because it is in the wrong position in the cells' chromosomes. Instead of its normal, quiet neighborhood, MYC finds itself adjacent to a gene known as the immunoglobulin gene. This busy gene is switched on by bits of DNA known as immunoglobulin enhancers, which normally prompt the cell to begin producing disease-fighting antibodies. In myeloma, the immunoglobulin enhancers act on the out-of-place MYC gene like an impatient finger at a doorbell, repeatedly activating it.

Researchers found that the enhancers are loaded with a "bromodomain" protein called BRD4, which, they demonstrate, is used to switch on MYC. Conveniently, it is targeted by JQ1. When investigators added JQ1 to laboratory samples of myeloma cells, the bromodomain proteins fell off the enhancers and the enhancers abruptly stopped working. The result: a shutdown of MYC and a slowdown of cancer cell division.

"In a sense, the JQ1 molecule cuts the cable that activates MYC and also connects MYC to the cell-growth genes," Bradner says. "The signal is interrupted and growth abruptly stops."

When investigators administered JQ1 to laboratory mice harboring myeloma cells, the disease receded and the animals lived longer than those that had not been treated. The study authors emphasize that JQ1 is a protytpe drug and cannot be used immediately to treat myeloma or other cancers. Its success in the current study illuminates the promise of JQ1-based therapies that target bromodomain proteins in cancers dependent on MYC for their growth.

"Together, our findings show that BRD4 has an important role in maintaining MYC activity in myeloma and other blood-related malignancies," says the study's senior author, Constantine Mitsiades, MD, of Dana-Farber. "They also point to the potential usefulness of drug-like bromodomain inhibitors as novel therapies against these diseases."

The study's lead authors are Jake Delmore and Ghayas Issa, MD, Dana-Farber. In addition to Bradner and Qi, the paper's other authors are Hannah Jacobs, Efstathios Kastritis, MD, Timothy Gilpatrick, Ronald Paranal, Anne Schinzel, Michael McKeown, Timothy Heffernan, PhD, Irene Ghobrial, MD, Paul Richardson, MD, William Hahn, MD, PhD, and Kenneth Anderson, MD, Dana-Farber; Andrew Kung, MD, PhD, and Madeleine Lemieux, PhD, Dana-Farber and Children's Hospital Boston; Peter Rahl, PhD, and Richard Young, PhD, Whitehead Institute for Biomedical Research, Cambridge, Mass.; Junwei Shi and Christopher Vakoc, MD, PhD, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY; and Marta Chesi, PhD, and P. Leif Bergsagel, MD, Mayo Clinic, Scottsdale, Arizona.

Financial support for the study was provided by the National Institutes of Health, the Chambers Medical Foundation, the Stepanian Fund for Myeloma Research, the Richard J. Corman Foundation, the Burroughs-Wellcome Fund, the Smith Family Award, the American Cancer Society, and the Damon Runyon Cancer Research Foundation.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. JakeE. Delmore, GhayasC. Issa, MadeleineE. Lemieux, PeterB. Rahl, Junwei Shi, HannahM. Jacobs, Efstathios Kastritis, Timothy Gilpatrick, RonaldM. Paranal, Jun Qi, Marta Chesi, AnnaC. Schinzel, MichaelR. McKeown, TimothyP. Heffernan, ChristopherR. Vakoc, P.Leif Bergsagel, IreneM. Ghobrial, PaulG. Richardson, RichardA. Young, WilliamC. Hahn, KennethC. Anderson, AndrewL. Kung, JamesE. Bradner, ConstantineS. Mitsiades. BET Bromodomain Inhibition asa Therapeutic Strategy to Target c-Myc. Cell, 2011; DOI: 10.1016/j.cell.2011.08.017

Cite This Page:

Dana-Farber Cancer Institute. "Novel approach scores first success against elusive cancer gene." ScienceDaily. ScienceDaily, 10 September 2011. <www.sciencedaily.com/releases/2011/09/110909111521.htm>.
Dana-Farber Cancer Institute. (2011, September 10). Novel approach scores first success against elusive cancer gene. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2011/09/110909111521.htm
Dana-Farber Cancer Institute. "Novel approach scores first success against elusive cancer gene." ScienceDaily. www.sciencedaily.com/releases/2011/09/110909111521.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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