The Radiosensitization of Cells Using the P56 Subunit of NF-ΚB
Section: For Industry
Category(ies): Cancer Therapeutics
Reference #: JUMI430504
OTC Contact: David Humphrey (Directory Information | Send a Message)
Description
Radiation therapy is currently one of the most common methods of treating cancer. Unfortunately, many cancers develop resistance to radiation during treatment, greatly reducing the efficacy of radiation therapy. Georgetown University is seeking a licensing partner for the development and commercialization of the use of NF-kappa B signaling pathway as a target for human tumor radiosensitization. NF-kappa B is a critical nuclear transcription factor that is activated in response to cellular stress. Constitutively elevated or dysregulated NF-kappa B activation leads to cell death in response to stress. NF-kappa B also plays an important role in a novel, radiation-inducible signaling pathway that involves the ataxia-telangiectasia mutated (ATM) protein kinase. Cells from patients with ataxia-telangiectasia (AT) are exquisitely sensitive to ionizing radiation and exhibit impaired NF-kappa B activation in response to this stress. Restoration of NF-kappa B regulation in AT fibroblasts by introducing a dominant negative form of I kappa B-alpha has resulted in correction of radiation sensitivity and a reduction of ionizing radiation-induced apoptosis.
Applications
Applications: The use of dominant negative cDNA or antisense cDNA of the p65 subunit of NF-kappa B has proven to be a powerful tool for sensitizing human cancers to ionizing radiation and for use in gene therapy.
Advantages:
- Expression of introduced ATM in AT cells results in correction of NF-kappa B regulation and an increase in postradiation survival without reduction in radiation-induced apoptosis.
- Cancers which have developed resistance to typical therapy can be sensitized to radiation therapy through control of the NF-kappa B pathway.
- Control of the NF-kappa B signaling pathway may also contribute to radiosensitivity syndrome and ataxia telangiectasia.
- NF-kappa B regulation can be used to control cellular apoptosis.
Advantages
Stage of Development
Stage of Development: Transfection of human squamous carcinoma cells with a dominant negative fragment of human p65 increases cellular radiosensitivity and radiation-induced apoptosis.
Inventors: Dr. Mira Jung and Dr. Anatoly Dritschilo, Department of Radiation Medicine
Relevant Publications
Relevant Publications: Kim et al. The p65 subunit of nuclear factor-kappaB is a molecular target for radiation sensitization of human squamous carcinoma cells. Mol. Cancer Ther. 3(6): 693-698, 2004.
Patent Status
U.S. Patent Application Publication 20050287158
