Navigation Links
Experimental drug could enhance multiple myeloma and myeloid leukemia therapies
Date:2/18/2014

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."


'/>"/>

Contact: John Wallace
wallacej@vcu.edu
804-628-1550
Virginia Commonwealth University
Source:Eurekalert  

Related medicine news :

1. Experimental Chemo Combo for Colon Cancer Disappoints
2. Experimental Pill for Multiple Sclerosis Shows Promise
3. Experimental Gel May Help Those With Advanced Parkinsons
4. Experimental Drug Eases Autistic Behaviors in Mice
5. Experimental Drug Helps Fight Some Childhood Cancers, Study Finds
6. Experimental drug improves muscle strength among male cancer patients
7. Experimental Vaccine Seems to Stop Nicotine Addiction in Mice
8. Content Writing King Announces Cancellation Of Experimental Video Creation Process For Their Article Marketing Website
9. Fertility preservation with cryopreservation of ovarian tissue: from experimental to mainstream
10. Experimental drug may extend therapeutic window for stroke
11. Experimental Chemical Helps Blind Mice See
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Experimental drug could enhance multiple myeloma and myeloid leukemia therapies
(Date:10/12/2017)... ... ... Asante, a nationally recognized health system in southern Oregon, ... health joint venture through an agreement, effective October 1, 2017, to create AccentCare ... company with Asante, delivering clinically integrated care, for the past eight years. This ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... has recently contributed a medical article to the newly revamped Cosmetic Town ... article spotlights the hair transplant procedure known as Follicular Unit Extraction ...
(Date:10/12/2017)... ... October 12, 2017 , ... Leading pediatric oncology experts ... Washington, D.C., for the 49th Congress of the International Society of Paediatric Oncology ... of the Center for Cancer and Blood Disorders at Children’s National, and ...
(Date:10/12/2017)... ... October 12, 2017 , ... Women-owned ... Michigan’s 2017 Best and Brightest in Wellness® by Best and Brightest. OnSite Wellness ... on Friday, Oct. 20 from 7:30 a.m. to 2 p.m. at the Henry ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... property taxes a year. In some states—like New York, New Jersey, Massachusetts, Texas, ... many overseas retirement havens have extremely low property-tax rates, which contributes to the ...
Breaking Medicine News(10 mins):
(Date:9/22/2017)... 22, 2017 AVACEN Medical (AVACEN) announced that ... successfully helping those with the widespread pain associated with ... Amanda in Essex, England commented, ... hair, experiencing no sleep at all, tremendous pain, with ... cannot recommend [the AVACEN 100] enough, how this has ...
(Date:9/19/2017)... 2017   ZirMed Inc ., a recognized leader in ... it has been ranked #1 by its users for the ... 2017 User Survey. ZirMed was recognized as the top-ranked end-to-end ... medical centers over 200 beds and holds one of the ... survey history. ...
(Date:9/18/2017)... , Sept. 18, 2017 EpiVax, ... of bioinformatics and immune engineering, today announced ... influenza A (H7N9) vaccine. ... to seasonal influenza and presents a challenge ... prior exposure to be effective. Using state-of-the-art ...
Breaking Medicine Technology: