Navigation Links
NCI renewal grant to develop new cancer therapies
Date:12/4/2007

Richmond, Va. (Dec. 4, 2007) – A Virginia Commonwealth University Massey Cancer Center research team has received a renewal grant totaling nearly $1.3 million from the National Cancer Institute to improve the activity of a novel class of agents, known as histone deacetylase inhibitors, in the treatment of leukemia and other blood malignancies.

Through the five-year grant, Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program, and his research team will focus efforts to support ongoing basic and clinical research.

Histone deacetylase inhibitors represent a diverse group of agents that modify the structure of chromatin, and by extension, genes involved in the control of death and differentiation in cancer cells. Chromatin houses the genome and is composed of DNA and scaffolding proteins, notably histones.

However, histone deacetylase inhibitors acetylate other proteins and exert multiple other effects which trigger apoptosis, or programmed cell death, in tumor cells. Acetylation is a chemical reaction that can change the molecular properties of certain proteins.

"Histone deacetylase inhibitors are currently the focus of intense interest as so-called ‘epigenetic agents,' that is, agents that act by modulating gene expression," said Grant, who is also the primary investigator for the project.

"Our goal is to exploit recent insights into the mode of action of these agents to make them even more effective in various hematologic malignancies by rationally combining them with other molecularly targeted agents," he said.

Recently, histone deacetylase inhibitors have been approved for the treatment of patients with cutaneous T cell lymphoma, a type of cancer of the immune system. In previous work, Grant's team has shown that histone deacetylase inhibitors induce acetylation and activation of a transcription factor, NF-kappaB, which regulates the expression of genes implicated in antioxidant defenses and cell survival.

According to Grant, the team has also identified agents that antagonize acetylation and activation of NF-kappa B by histone deacetylase inhibitors, resulting in a dramatic increase in oxidative injury and lethality. Such agents include inhibitors of IKK-beta and a class of agents known as proteasome inhibitors. Further, proteasome inhibitors have already proven very active in multiple myeloma and certain types of lymphoma, said Grant.

"Our goal is to elucidate the mechanisms by which such agents increase histone deacetylase inhibitor activity against leukemia and related malignancies," Grant said.

"We can then utilize this information as a platform to develop novel combination regimens incorporating histone deacetylase inhibitors and NF-kappa B antagonists such as proteasome and IKK beta inhibitors in the treatment of acute leukemia and other hematologic malignancies."

Grant and his team are already leading a multi-institutional trial of vorinostat, a histone deacetylase inhibitor, in combination with flavopiridol, a cell cycle inhibitor, in patients with refractory acute leukemia or myelodysplastic syndrome.

Additionally, the team has recently received approval to lead a multi-institutional trial of vorinostat and bortezomib, a proteasome inhibitor, in patients with refractory diffuse lymphocytic B-cell lymphoma or mantle cell lymphoma.


'/>"/>

Contact: Sathya Achia-Abraham
sbachia@vcu.edu
804-827-0890
Virginia Commonwealth University
Source:Eurekalert

Related biology news :

1. UCs NIH grant brings technology from outer space to playgrounds
2. Seattle Childrens Hospital leads $23.7 million NIH grant to study gene repair
3. Homeland Security awards 2 grants to Rutgers for nuclear threat detection
4. NIH awards researcher $1.5 million new innovator grant for fruit-fly studies of prion proteins
5. UGA Odum School of Ecology professor receives grant to study West Nile Virus in NYC
6. Genes and environment grant funds close look at nature-nurture overlap in common diseases
7. Mustafa alAbsi Ph.D. and national team awarded major NIH grant
8. NIH awards UC $9 million grant to improve patient point-of-care technologies
9. UAB wins $5.7M neurofibromatosis grant
10. Flu vaccine in painless skin patches under development at Emory, Georgia Tech with NIH grants
11. Study reveals that immigrant teenagers eat better than Spanish teenagers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/12/2017)... , Jan. 12, 2017  Trovagene, Inc. (NASDAQ: ... (ctDNA) technologies, today announced that it has signed agreements ... and the Middle East ... milestone marks the first wave of international distribution agreements ... and blood samples. The initial partners will ...
(Date:1/11/2017)... MOINES, Iowa , Jan. 11, 2017 ... industry first with the release of its patent-pending calibration ... quickly and reliably perform calibrations, securely upload data logs ... flexibility for the customer. "Fighting drunk driving ... only for the public at large, but also for ...
(Date:1/6/2017)...  SomaLogic announced today that it has agreed ... iCarbonX, the China -based company ... Health Ecosystem that can define each person,s ,digital ... behavioral and psychological data, the Internet and artificial ... will provide proteomics data and applications expertise to ...
Breaking Biology News(10 mins):
(Date:1/19/2017)... Berkeley, CA (PRWEB) , ... January 19, 2017 ... ... the delivery of product vigilance software to leading biopharmaceutical and medical device manufacturers ... Mail is a fully 21 CFR Part 11-compliant email client designed to provide ...
(Date:1/19/2017)... ... January 18, 2017 , ... The American Medical Informatics ... its Data Sharing Policy. Specifically, the nation’s leading informatics experts, said data sharing ... existing policy. AMIA recommended that NIH earmark funding for researchers to produce and ...
(Date:1/19/2017)... The global biotechnology services outsourcing market ... 2025, according to a new report by Grand ... of the function of outsourcing certain clinical and ... services outsourced, clinical trial management and contract manufacturing ... was the first pharmaceutical company to outsource its ...
(Date:1/18/2017)... ... January 18, 2017 , ... ... interconnect using USB or PCI Express, announced the ZEM5310 USB 3.0 FPGA Module, ... into a compact business-card sized form factor suitable for prototyping, testing, and production-ready ...
Breaking Biology Technology: