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:6/25/2016)... ... 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due to a ... new, often overlooked aspect of head lice: the parasite’s ability to live away from a ... occurrence, but a necessary one in the event that lice have simply gotten out of ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van ... Wellness at Work award to iHire in recognition of their exemplary accomplishments in worksite ... 7th annual Maryland Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum ...
(Date:6/24/2016)... ... ... was in a crisis. Her son James, eight, was out of control. Prone to extreme ... “When something upset him, he couldn’t control his emotions,” remembers Marcy. “If there was ... other children and say he was going to kill them. If we were driving ...
(Date:6/24/2016)... Rhinebeck, NY (PRWEB) , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of ... of companies that call for a minimum wage raise to $12 an hour by 2020 ... wage. This will restore the lost value of the minimum wage, assure the wage floor ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... actively feeding the Frederick area economy by obtaining investment capital for emerging technology ... past 2½ years that have already resulted in more than a million dollars ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016   Pulmatrix, Inc ., ... developing innovative inhaled drugs, announced today that it was ... Investments reconstituted its comprehensive set of U.S. and ... "This is an important milestone for Pulmatrix," said Chief ... shareholder awareness of our progress in developing drugs for ...
(Date:6/23/2016)... 23, 2016 Research and Markets has ... - Forecast to 2022" report to their offering. ... for the patients with kidney failure, it replaces the function ... the patient,s blood and thus the treatment helps to keep ... in balance. Increasing number of ESRD patients ...
(Date:6/23/2016)... June 23, 2016 Roche (SIX: RO, ROG; ... for its Elecsys BRAHMS PCT (procalcitonin) assay as a ... septic shock. With this clearance, Roche is the first ... integrated solution for sepsis risk assessment and management. ... infection and PCT levels in blood can aid clinicians ...
Breaking Medicine Technology: