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Investigators at the NCI Laboratory of Immune Cell Biology discovered an Anti-TNF Induced Apoptosis (ATIA) protein, which protects cells against apoptosis. ATIA is highly expressed in glioblastoma and astrocytomas and its inhibition results in increased cell sensitivity to TNF-related apoptosis-inducing ligand induced cell death. Hence, ATIA assays may enable clinicians to effectively stratify patients for appropriate treatment. ATIA exists in a soluble form that can be detected in culture medium of ATIA expressing cells indicating it could be used to develop a non-invasive, blood based diagnostic test such as an ELISA. Glioblastomas and astrocytomas can be diagnosed via MRI and CT scans; however, these scans cannot detect tumor type, i.e. glioblastoma vs. medulloblastoma. Our recent study suggests that ATIA is induced in cells under hypoxia conditions. More importantly, knockdown of ATIA in human glioblastoma cells renders cells to apoptosis under hypoxia conditions. Therefore, ATIA is a potential novel therapeutic target for treating human glioblastoma.
Glioblastoma arise from astrocytes, cells that provide neurons structural and metabolic support. Glioblastomas account for twenty percent of primary brain tumors and fifty percent of astrocytomas. These indications are designated as rare diseases as there is an annual 2-3 newly diagnosed cases of glioblastoma per 100,000 people in the United States whereas the astrocytoma incidence rate is 1.22 cases per 100,000 for individuals aged 0-19 years in the United States.
Discovery (Lead Identification)
Licensing and research collaboration
Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...