Featured Research

from universities, journals, and other organizations

Predicting therapy outcomes in prostate cancer with bone metastasis

Date:
May 1, 2014
Source:
American Association for Cancer Research (AACR)
Summary:
A new computational model that simulates bone metastasis of prostate cancer has the potential to rapidly assess experimental therapy outcomes and help develop personalized medicine for patients with this disease, according to data. The researchers found that when they introduced a single metastatic prostate cancer cell to the model, it was able to simulate bone metastasis seven out of 25 times, accurately creating the vicious cycle. This phenomenon is difficult to reproduce using preclinical animal models, which is critical in determining the best time to apply therapies in order to obtain maximum efficiency, they explained.

A new computational model that simulates bone metastasis of prostate cancer has the potential to rapidly assess experimental therapy outcomes and help develop personalized medicine for patients with this disease, according to data published in Cancer Research, a journal of the American Association for Cancer Research.

"Bone remodeling is a balanced and extremely well regulated process that controls the health of our bones and the levels of circulating calcium," said Leah M. Cook, Ph.D., postdoctoral fellow in the Department of Tumor Biology at the Moffitt Cancer Center in Tampa, Fla. "Active prostate cancer cells in the bone environment can speak the same language of the bone remodeling cells, and disrupt the delicate bone remodeling process. They promote extensive bone destruction and formation that in turn yields nutrients, allowing the prostate cancer cells to grow, thus creating a vicious cycle."

"The mathematical model we created simulates this vicious cycle, and allows us to predict the impact of potential therapies on cancer cells and normal cells of the bone," said Arturo Araujo, Ph.D., postdoctoral fellow in the Department of Integrated Mathematical Oncology at the Moffitt Cancer Center. "Unlike biological models, we can freeze the mathematical model at any time point in order to explore what each cell is doing at that particular point in time."

To create the computational model, which they call "hybrid cellular automata," Araujo, Cook, and colleagues created simulations of different cell types involved in bone metastasis of prostate cancer, including two types of bone cells called osteoclasts and osteoblasts, and prostate cancer cells. They then created algorithms to simulate the interactions of these cells among themselves and with other bone metastasis-related factors in the microenvironment, including the proteins TGF-beta, RANKL, and other bone-derived factors.

The researchers found that when they introduced a single metastatic prostate cancer cell to the model, it was able to simulate bone metastasis seven out of 25 times, accurately creating the vicious cycle. This phenomenon is difficult to reproduce using preclinical animal models, which is critical in determining the best time to apply therapies in order to obtain maximum efficiency, explained Araujo.

Further, the fact that the model failed to generate a bone lesion 18 out of 25 times reflects reality, where not every metastatic cancer cell that invades bone in prostate cancer patients succeeds in forming a viable lesion, he added.

In parallel to developing the computational model, the researchers grew prostate cancer cells that metastasize to bone in mice and found that the tumor growth rate predicted by the computational model was comparable to the tumor growth rate in mice, thus validating their simulations. The model was also able to identify some critical players and events in the process of bone metastasis.

To test if the model could predict treatment outcomes, they applied two standard-of-care treatments, bisphosphonates and an anti-RANKL therapy, and found that the anti-RANKL therapy fared better than bisphosphonates, which is what is seen in prostate cancer patients with bone metastasis treated with these therapies, according to Araujo. The model predicted that improving the efficacy of anti-RANKL delivery to the prostate cancer-bone microenvironment might yield better outcomes.

With further improvements, the model can be individualized to determine personalized medicine for prostate cancer patients, Araujo noted.

"By integrating mathematics with robust biological data, we are beginning to develop powerful tools that allow us to rapidly assess how factors contribute to prostate cancer progression in bone," said Araujo. "Ultimately, we feel that the ability to customize these models based on inputs from each patient's cancer biopsy will help medical oncologists determine the best treatment strategies, so that significant improvements in survival and quality of life can be made."


Story Source:

The above story is based on materials provided by American Association for Cancer Research (AACR). Note: Materials may be edited for content and length.


Journal Reference:

  1. A. Araujo, L. M. Cook, C. C. Lynch, D. Basanta. An Integrated Computational Model of the Bone Microenvironment in Bone-Metastatic Prostate Cancer. Cancer Research, 2014; 74 (9): 2391 DOI: 10.1158/0008-5472.CAN-13-2652

Cite This Page:

American Association for Cancer Research (AACR). "Predicting therapy outcomes in prostate cancer with bone metastasis." ScienceDaily. ScienceDaily, 1 May 2014. <www.sciencedaily.com/releases/2014/05/140501075051.htm>.
American Association for Cancer Research (AACR). (2014, May 1). Predicting therapy outcomes in prostate cancer with bone metastasis. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2014/05/140501075051.htm
American Association for Cancer Research (AACR). "Predicting therapy outcomes in prostate cancer with bone metastasis." ScienceDaily. www.sciencedaily.com/releases/2014/05/140501075051.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. 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