Featured Research

from universities, journals, and other organizations

Roadmap published for dynamic mapping of estrogen signaling in breast cancer

Date:
June 17, 2011
Source:
Georgetown University Medical Center
Summary:
The first roadmap to mathematical modeling of a powerful basic "decision circuit" in breast cancer has been developed. The preliminary mathematical model is the first result of work to develop a systems approach to understanding and treating one of the most common forms of breast cancer.

The first roadmap to mathematical modeling of a powerful basic "decision circuit" in breast cancer has been developed and published in Nature Reviews Cancer.

The preliminary mathematical model is the first result of a $7.5 million federal grant, awarded to scientists at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC) and collaborators at Virginia Tech and Fox Chase Cancer Center, to develop a systems approach to understanding and treating one of the most common forms of breast cancer.

"A cell is an information processing system and cancer cells make decisions that promote their growth, so we are striving to understand how these cells make mathematically-based choices based on inputs, processing, and outputs," says lead investigator Robert Clarke, PhD, DSc, a professor of oncology at Lombardi and GUMC's newly appointed Dean for Research.

The model, which is being built in modules, is designed to understand estrogen signaling in breast cancer cells, and by extension, why some cancer cells are susceptible to endocrine therapy while others are not. The estrogen hormone drives over half of the 180,000 cases of invasive breast cancer diagnosed each year, yet endocrine therapies designed to shut down this growth pathway are not as successful as simpler, human-derived models would have predicted, Clarke says.

"We need an engineering approach to a biological problem, and this is a very novel, and promising, start," says Clarke. "No one has built a model of breast cancer cell fate decision- making like this before."

His colleagues in this endeavor are Louis M. Weiner, MD, director of the Lombardi Comprehensive Cancer Center; John J. Tyson, PhD, first author of this study, as well as a computational cell biologist and professor at Virginia Tech; and William T Baumann, PhD, an electrical and computer engineer and associate professor at Virginia Tech. Tyson and Baumann have assembled a team of graduate students and postdoctoral researchers to assist in the modeling project.

"We are providing a roadmap of how a modeler might capture, in mathematical form, the molecular events controlling cell growth, proliferation, damage responses, and programmed cell death," says Tyson. "The value of this enterprise will be measured ultimately by new insights provided by the model into the logic and functionality of estrogen-receptor signaling and by the effectiveness of the model as a tool for experimental prediction and design."

Although scientists have amassed a large body of information about the genes and proteins involved in pathways that govern cancer development and growth, and based on that, have developed some "good ideas about how they go awry in certain cancers, most of our understanding relies on intuitive reasoning about highly complex networks of biochemical interactions," the researchers say in their study. "Wouldn't it be better if we could frame a reaction network in precise mathematical terms and use computer simulation to work out the implications of how the network functions in normal cells and malfunctions in cancer cells?"

"The hallmark of cancer cells is that they are making decisions that are right for them, not for the survival of the human organism, so we need to understand those choices," Clarke says.

The roadmap detailed in Nature Reviews Cancer is built on the idea that a cell is an information processing system, receiving signals from its environment and its own internal state, interpreting those signals, and making appropriate cell-fate decisions, such as growth and division, movement, differentiation, self-replication, or cell death.

To that end, the investigators have already begun to model separate modules that computers can track in terms of the dynamic consequences of multiple and often conflicting interactions. These include "decision modules" (cell cycle and apoptosis), "stress modules" (autophagy and unfolded protein response), and the "signal processing modules" (estrogen receptor and growth factor signaling transduction networks).

Clarke says that a lot of "wet lab work" data from Lombardi laboratories, measuring how changes in gene and protein expression affects response to endocrine therapy, is being transferred into the model, along with published information from other institutions.

Not only does the model have the potential to explain why certain subtypes of breast cancer respond or become resistant to endocrine therapy, it could be used to help test potential new therapies, he says.

"If we tweak some gene in the model and all the breast cancer cells die, we can go back to the lab and test if that actually occurs," Clarke says. "That means that once we understand the decisions that these cancer cells are making, we have an efficient way of developing drugs or combination of drugs."

"The hard work is yet to be done, but it is just a matter a time before an effective, integrated model of regulatory networks in breast cancer cells is informing the next wave of experiments and therapies," says Tyson.


Story Source:

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


Journal Reference:

  1. John J. Tyson, William T. Baumann, Chun Chen, Anael Verdugo, Iman Tavassoly, Yue Wang, Louis M. Weiner & Robert Clarke. Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells. Nature Reviews Cancer., 16 June 2011 DOI: 10.1038/nrc3081

Cite This Page:

Georgetown University Medical Center. "Roadmap published for dynamic mapping of estrogen signaling in breast cancer." ScienceDaily. ScienceDaily, 17 June 2011. <www.sciencedaily.com/releases/2011/06/110616092654.htm>.
Georgetown University Medical Center. (2011, June 17). Roadmap published for dynamic mapping of estrogen signaling in breast cancer. ScienceDaily. Retrieved April 25, 2014 from www.sciencedaily.com/releases/2011/06/110616092654.htm
Georgetown University Medical Center. "Roadmap published for dynamic mapping of estrogen signaling in breast cancer." ScienceDaily. www.sciencedaily.com/releases/2011/06/110616092654.htm (accessed April 25, 2014).

Share This



More Health & Medicine News

Friday, April 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Fungus Killing Bats, Spreading in US

Deadly Fungus Killing Bats, Spreading in US

AP (Apr. 24, 2014) A disease that has killed more than six million cave-dwelling bats in the United States is on the move and wildlife biologists are worried. White Nose Syndrome, discovered in New York in 2006, has now spread to 25 states. (April 24) Video provided by AP
Powered by NewsLook.com
Companies Ramp Up Wellness to Lower Health Costs

Companies Ramp Up Wellness to Lower Health Costs

AP (Apr. 24, 2014) That little voice telling you to exercise, get in shape and get healthy is probably coming from your boss. More companies are beefing up wellness programs to try and cut down their health care costs. (April 24) Video provided by AP
Powered by NewsLook.com
Blood From World's Oldest Woman Suggests Life Limit

Blood From World's Oldest Woman Suggests Life Limit

Newsy (Apr. 24, 2014) Scientists say for the extremely elderly, their stem cells might reach a state of exhaustion. This could limit one's life span. Video provided by Newsy
Powered by NewsLook.com
FDA Wants To Ban Sales Of E-Cigarettes To Minors

FDA Wants To Ban Sales Of E-Cigarettes To Minors

Newsy (Apr. 24, 2014) The Food and Drug Administration wants to crack down on the use of e-cigarettes, banning the sale of the product to minors. 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:
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