Featured Research

from universities, journals, and other organizations

Multiple myeloma, myeloid leukemia therapies could be enhanced by experimental drug

Date:
February 18, 2014
Source:
Virginia Commonwealth University
Summary:
An experimental drug known as dinaciclib could improve the effectiveness of certain multiple myeloma and myeloid leukemia therapies, a pre-clinical study suggests. The study showed that dinaciclib disrupted a cell survival mechanism known as the unfolded protein response (UPR). Without the UPR, multiple myeloma and myeloid leukemia cells were unable to combat damage caused by some anti-cancer agents. Dinaciclib is a member of a class of drugs known as cyclin-dependent kinase (CDK) inhibitors. CDKs regulate a series of events known as the cell cycle, or cell-division cycle, that lead to the division and duplication of cells.

A pre-clinical study led by Virginia Commonwealth University Massey Cancer Center and Department of Internal Medicine researchers suggests that an experimental drug known as dinaciclib could improve the effectiveness of certain multiple myeloma and myeloid leukemia therapies. The study, recently published in the journal Molecular Cancer Therapeutics, showed that dinaciclib disrupted a cell survival mechanism known as the unfolded protein response (UPR). Without the UPR, multiple myeloma and myeloid leukemia cells were unable to combat damage caused by some anti-cancer agents.

"Although dinaciclib has shown promising pre-clinical activity against a variety of tumor cells, and is currently undergoing phase I/II clinical trials in several malignancies, the mechanisms responsible for its anti-tumor activity are not fully understood," says the study's lead investigator Steven Grant, M.D., associate director for translational research, co-leader of the Developmental Therapeutics research program and Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research at Massey. "Our research highlights a potentially new mechanism of dinaciclib action, and raises the possibility that this agent could be a useful addition to current multiple myeloma and myeloid leukemia therapies."

Dinaciclib is a member of a class of drugs known as cyclin-dependent kinase (CDK) inhibitors. CDKs regulate a series of events known as the cell cycle, or cell-division cycle, that lead to the division and duplication of cells. In many cancers, CDKs are overactive or CDK-inhibiting proteins are not functional, which results in the unregulated proliferation of cancer cells. Laboratory observations from this study suggest that two specific CDKs, CDK1 and CDK5, play key roles in regulating the UPR by helping to control the production and accumulation of a protein known as X-box binding pretein-1 (XBP-1).

The spliced form of XBP-1 (XBP-1s) helps regulate the expression of genes critical to cellular stress responses. External stressors, including certain anti-cancer agents, can cause mis-folded proteins to accumulate in the endoplasmic reticulum (ER), an interconnected network of sacs and tubules that manufacture, process and transport a variety of compounds important for cell survival. These stressors can also cause XBP-1s to accumulate in the cell's nucleus, which promotes the UPR and helps cells withstand the damaging effects of mis-folded proteins. The scientists discovered that dinaciclib, by interfering with UPR activation, caused multiple myeloma and myeloid leukemia cells to initiate a form of cell suicide known as apoptosis when exposed to agents that induced ER stress.

"These findings build on a long history of work in our laboratory investigating mechanisms by which cancer cells respond to environmental stresses," says Grant. "We intend to continue investigating ways in which dinaciclib and other CDK inhibitors might be used to disrupt the UPR and potentially improve the effectiveness of certain agents for the treatment of multiple myeloma or myeloid leukemia."


Story Source:

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


Journal Reference:

  1. T. K. Nguyen, S. Grant. Dinaciclib (SCH727665) inhibits the unfolded protein response (UPR) through a CDK1 and CDK5-dependent mechanism. Molecular Cancer Therapeutics, 2013; DOI: 10.1158/1535-7163.MCT-13-0714

Cite This Page:

Virginia Commonwealth University. "Multiple myeloma, myeloid leukemia therapies could be enhanced by experimental drug." ScienceDaily. ScienceDaily, 18 February 2014. <www.sciencedaily.com/releases/2014/02/140218114309.htm>.
Virginia Commonwealth University. (2014, February 18). Multiple myeloma, myeloid leukemia therapies could be enhanced by experimental drug. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2014/02/140218114309.htm
Virginia Commonwealth University. "Multiple myeloma, myeloid leukemia therapies could be enhanced by experimental drug." ScienceDaily. www.sciencedaily.com/releases/2014/02/140218114309.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
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