Featured Research

from universities, journals, and other organizations

Advances in understanding of the mechanisms of drug resistance to dual-agent chemotherapy in recurrent ovarian cancer

Date:
November 30, 2012
Source:
BioMed Central Limited
Summary:
More than half of all patients with ovarian cancer experience recurrent disease and will eventually fail to respond to chemotherapy. The failure of chemotherapy is usually due to the development of resistance to the two main classes of chemotherapy agents used to fight it – platinating agents and taxanes. Now, a new study provides novel information that further adds to clinicians’ understanding of the mechanisms involved in the development of resistance to dual-agent chemotherapy.

More than half of all patients with ovarian cancer experience recurrent disease and will eventually fail to respond to chemotherapy. The failure of chemotherapy is usually due to the development of resistance to the two main classes of chemotherapy agents used to fight it -- platinating agents and taxanes. Now, a study reported in the open-access Journal of Ovarian Research provides novel information that further adds to clinicians' understanding of the mechanisms involved in the development of resistance to dual-agent chemotherapy.

It was not known whether mechanisms of resistance to dual-agent chemotherapy are a combination of single-agent resistance responses or if novel mechanisms arise as a result of combined platinating agent/taxane therapy. Carita Lanner and her team, from Sudbury, Ontario, in Canada, provide evidence to suggest that the latter is true: novel and different changes occur to cause resistance to the dual combination of agents.

Ovarian cancer is the most lethal gynecological cancer, with a 5-year mortality rate of over 50%. A significant contributing factor to the high mortality rate is the development of resistance to chemotherapy regimens. The differences in mode of action and mechanisms of resistance for platinating agents and taxanes are taken advantage of in dual-agent chemotherapy of advanced cancer. Used together, they achieve increased efficacy and progression-free survival in patients. However, combined resistance to both agents may occur, and is more difficult to overcome than single-agent resistance.

Lanner and colleagues set out to investigate if the development of dual agent resistance invokes different mechanisms or is a combination of the mechanisms of resistance that arise upon exposure to single agents. To do this, they developed a set of isogenic ovarian cancer cell lines resistant to either (1) the platinating agent carboplatin, (2) the taxane docetaxel, or (3) a combination of carboplatin and docetaxel. They analyzed changes in gene expression associated with the specified drug resistance in each cell line using microarray analysis.

The team compared the three resistant cell lines to identify shared and different changes in gene expression amongst all three treatments. The analysis showed that the establishment of carboplatin and docetaxel resistance did not share many changes in gene expression. Most significantly, dual-agent resistance appeared to develop from mostly unique changes in gene expression, different from both single carboplatin and docetaxel resistance in the set of isogenic cell lines studied.

Lead author Carita Lanner commented, "These results demonstrate that combined drug resistance is NOT just a combination of changes present in single agent-resistant cells but contains different and new changes. The dual carboplatin-docetaxel resistant cell line will facilitate further investigation into mechanisms underlying the development of dual drug resistance in ovarian cancer."


Story Source:

The above story is based on materials provided by BioMed Central Limited. Note: Materials may be edited for content and length.


Journal Reference:

  1. Stephen R Armstrong, Rashmi Narendrula, Baoqing Guo, Amadeo M Parissenti, Katherine L McCallum, Stephanie Cull, Carita Lannιr. Distinct genetic alterations occur in ovarian tumor cells selected for combined resistance to carboplatin and docetaxel. Journal of Ovarian Research, 2012; 5 (1): 40 DOI: 10.1186/1757-2215-5-40

Cite This Page:

BioMed Central Limited. "Advances in understanding of the mechanisms of drug resistance to dual-agent chemotherapy in recurrent ovarian cancer." ScienceDaily. ScienceDaily, 30 November 2012. <www.sciencedaily.com/releases/2012/11/121129232613.htm>.
BioMed Central Limited. (2012, November 30). Advances in understanding of the mechanisms of drug resistance to dual-agent chemotherapy in recurrent ovarian cancer. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2012/11/121129232613.htm
BioMed Central Limited. "Advances in understanding of the mechanisms of drug resistance to dual-agent chemotherapy in recurrent ovarian cancer." ScienceDaily. www.sciencedaily.com/releases/2012/11/121129232613.htm (accessed April 24, 2014).

Share This



More Health & Medicine News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) — Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) — A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) — Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) — NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. 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