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:2/12/2016)... ... 12, 2016 , ... Young Asset Protection, a full service ... the latest charity campaign in their community enrichment program. Art Expression utilizes after-school ... cause are currently being accepted at: http://artexpressioninc.org/ . , Art Expression is ...
(Date:2/12/2016)... ... February 12, 2016 , ... J Thomas ... by continuing it’s commitment to act as Agents of Change in the community, ... with area homeless families to fulfill immediate needs and help them move into ...
(Date:2/12/2016)... Pa. (PRWEB) , ... February 12, 2016 , ... ... sort through a world of exterior design possibilities. CertainTeed, North America’s leading brand ... tools by expanding the product offerings showcased in the mobile version of the ...
(Date:2/12/2016)... ... February 12, 2016 , ... The Central Coast Autism Spectrum Center (CCASC) invites teens ages 11-18 ... night of fun for teens with and without special needs to gather in a safe ... the event. The dance will take place on Saturday, Feb. 13 from 7 to 9:30 ...
(Date:2/12/2016)... CA (PRWEB) , ... February 12, 2016 , ... ... Film Studios. The new cartoon style themes are great for showcasing pictures, videos as ... customized scene generators, titles like introductions, lower thirds, transitions and a beautiful frame overlay. ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... 12, 2016  Innophos Holdings, Inc. (NASDAQ: IPHS ), ... today announced that it will host a live conference call ... discuss its fourth quarter and full year 2015 results. ... release detailing fourth quarter and full year results will be ... --> --> The conference ...
(Date:2/12/2016)... -- SI-BONE, Inc., a medical device company that pioneered the use of ... (MIS) device indicated for fusion for certain disorders of the sacroiliac ... Administrative Contractor (MAC) covering the states of Connecticut ... Massachusetts , Minnesota , ... Rhode Island , Vermont ...
(Date:2/12/2016)... 2016 On Thursday, Feb. 11, 2016, surgeons ... David,s North Austin Medical Center successfully completed the first ... ® Surgical System with Trumpf Medical,s advanced operating ... Lakshman , M.D., colorectal surgeon at the Texas Institute ... Table Motion technology, which seamlessly combines the da Vinci ...
Breaking Medicine Technology: