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:1/21/2016)... , January 21, 2016 ... a new market research report "Emotion Detection and Recognition ... Software Tools (Facial Expression, Voice Recognition and Others), ... Global forecast to 2020", published by MarketsandMarkets, the ... to reach USD 22.65 Billion by 2020, at ...
(Date:1/20/2016)... 20, 2016   MedNet Solutions , an innovative ... of clinical research, is pleased to announce the attainment ... are the result of the company,s laser focus on ... , it,s comprehensive, easy-to-use and highly affordable cloud-based ... Key MedNet growth achievements in 2015 include: ...
(Date:1/18/2016)... , Jan. 18, 2016  Extenua Inc., a ... simplifies the use and access of ubiquitous on-premise ... partnership with American Cyber.  ... experience leading transformational C4ISR and Cyber initiatives in ... the latest proven technology solutions," said Steve ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... , Germany and ... QGEN ; Frankfurt Prime Standard: QIA) today ... Targeted RNA Panels for gene expression profiling, expanding QIAGEN,s ... (NGS). The panels enable researchers to select from over ... changes and discover interactions between genes, cellular phenotypes and ...
(Date:2/11/2016)... , Feb. 11, 2016  Spectra BioPharma Selling ... (CSO) that provides biopharma companies the experience, expertise, ... and deploy outsourced sales teams. Created in concert ... addresses both the strategic and tactical needs of ... sales solutions through both personal and non-personal promotion. ...
(Date:2/11/2016)... , ... February 11, 2016 ... ... publication dedicated to delivering cutting-edge information focused on the development and manufacture ... to become a premier sponsor of the 2016 BioProcess International Awards – ...
(Date:2/11/2016)... February 11, 2016 ... or "Company") (OTCQB: PSID), a life sciences company ... its Thermomedics subsidiary, which markets the Caregiver® FDA-cleared ... plan in January 2016, including entering into agreements ... monthly sales growth, and establishing several near-term pipeline ...
Breaking Biology Technology: