Navigation Links
Inhibition of CDK4 might promote lymphoma development and progression
Date:3/20/2014

COLUMBUS, Ohio Anticancer agents that inhibit tumor growth by targeting a regulatory protein called CDK4 might actually promote the development and progression of certain B-cell lymphomas, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James).

The study indicates that inhibiting CDK4, a regulator of the cell cycle, promotes genetic instability and the development or progression of B-cell lymphomas that are driven by the MYC oncogene.

The research suggests that CDK4 inhibitors, which are now in clinical testing, should be used cautiously, particularly in patients with B-cell lymphomas. The findings also raise the possibility that these inhibitors work through off-target effects and require further investigation.

The study is published in The Journal of Clinical Investigation.

"Anti-CDK4 strategies are being widely tested as broad-spectrum anticancer therapies," says study leader Xianghong Zou, PhD, assistant professor of medicine and a member of the OSUCCC James Molecular Carcinogenesis and Chemoprevention Program. Zou's collaborators on the research included John Cleveland, PhD, professor and chair of cancer biology at The Scripps Research Institute.

"Our findings indicate that anti-CDK4 strategies must be carefully tailored because they might have unexpected lymphoma-promoting effects," Zou says.

"It was quite striking," he adds. "Silencing Cdk4 in our mouse model and in human B-cell lymphoma cells had the opposite effect of small-molecule inhibitors that are touted as selective inhibitors of CDK4 and CDK6," he says.

"Given that these agents have undergone limited profiling, it might be that these agents inhibit kinases other than CDK4, and that in lymphoma cells they promote critical factors that support cell growth and survival."

For this study, Zou and his colleagues used a mouse model of MYC-driven B-cell lymphoma they had developed earlier, and human cell lines of Burkitt and other non-Hodgkin lymphomas.

Key technical findings include:

  • Although CDK4 functions as an oncogene in breast and other cancers, loss of CDK4 can greatly promote cancer onset and growth in a model of MYC-driven B-cell lymphoma and in human B-cell lymphoma cells;

  • The lymphoma-promoting effects of the experimental CDK4 deficiency were associated with dysregulation of a gene pathway that leads to genomic instability;

  • CDK4 deficiency leads to lymphomas with major genomic alterations that are associated with the dysregulation of genes that are known to promote cancer.


'/>"/>
Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University Wexner Medical Center
Source:Eurekalert

Related medicine news :

1. Specific inhibition of autophagy may represent a new concept for treatment of kidney cancer
2. Treating drug resistant cancer through targeted inhibition of sphingosine kinase
3. Novel test identifies patients most likely to benefit from ALK inhibition therapy
4. Neurological Wellness Center's Novel Neuro-Inflammation Inhibition Procedure that Induces Rapid Recovery from Alzheimer's, Stroke and Brain Injury is Now Being Taught in a Newly Released Video
5. Epoxide hydrolase inhibition and Thiazolidinediones: A therapy for cardiometabolic syndrome
6. New STELARA data show inhibition of joint destruction in active psoriatic arthritis
7. Inhibition of oral biofilm and cell-cell communication using natural-products derivatives
8. New Stool Test Might Aid in Early Detection of Colon Cancer
9. Depo-Provera Birth Control Might Raise Breast Cancer Risk
10. Brain Falters Near End of Life, but Games, Puzzles Might Slow Decline
11. Infection Might Raise Blood Clot Risk for Older Adults: Study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/23/2017)... ... ... The Military Officers Association of America (MOAA) announced its support for the ... Col. Thomas G. Bowman. , Bowman currently serves as the staff director for the ... issues and challenges veterans face with the VA. Following a 30-year career of service ...
(Date:6/23/2017)... ... June 23, 2017 , ... Everybody has their own personal preference ... to read it, and some people don't like it at all. FindaTopDoc took a ... found: , Erotic literature can give readers a taste of their deepest, darkest fantasies ...
(Date:6/23/2017)... (PRWEB) , ... June 23, 2017 , ... ... cooking is essential, and two new videos highlight the importance of correctly using ... Christine Bruhn, Ph.D., who has done extensive research on consumer food safety habits. ...
(Date:6/23/2017)... FL (PRWEB) , ... June 23, 2017 , ... ... Pinecrest, Florida. This is MD Now’s 28th facility overall and marks the urgent care ... Highway, located one mile North of The Falls shopping mall. The new clinic offers ...
(Date:6/23/2017)... ... June 23, 2017 , ... American Farmer, will feature ... which is slated to air fourth quarter 2017. American Farmer airs Tuesdays at 8:30aET ... a Danish pharmacist, founded Chr. Hansen in Denmark in 1874 after a groundbreaking discovery ...
Breaking Medicine News(10 mins):
(Date:6/5/2017)... Cincinnati location of Diplomat Specialty Infusion ... been awarded a Top Workplaces 2017 honor by ... on an employee survey administered by WorkplaceDynamics, LLC, a research ... measures several aspects of workplace culture, including alignment, execution, and ... ...
(Date:6/2/2017)... , June 2, 2017  NxStage Medical, Inc. (Nasdaq: ... care, today announced new findings demonstrating positive biochemical outcomes ... System One™. The data will be presented at ... Madrid, Spain . ... Improve Home Dialysis Network in Europe ...
(Date:5/30/2017)... Holdings, Inc. (NYSE: HRC), will present at the Goldman Sachs ... 13, 2017, in Rancho Palos Verdes, California ... officer, is scheduled to present at 3:20 p.m. Pacific Time. ... http://ir.hill-rom.com/events.cfm . A recorded replay will be available one ... 2017. About Hill-Rom ...
Breaking Medicine Technology: