Researchers at the NCI Radiation Oncology Branch and NIH CIT Center for Molecular Modeling developed a tetrahydroxamate chelation technology that provides a more-stable Zr-89 complex as an immuno-PET cancer imaging agent. In either the linear or the macrocyclic form, the tetrahydroxamate complexes exhibit greater stability as chelating agents compared to Zr-89 complexed to the siderophore desferrioxamine B (DFB), a trihydroxamate, which represent
GATA-3 is a transcription factor that is highly expressed in normal cells of the mammary luminal epithelium. GATA-3 plays a regulatory role in determining the fate of cells in the mammary gland. Disruption of GATA-3 expression leads to defects in the development of mammary cells, including an inability to differentiate properly into the correct cell type. GATA-3 function is also disrupted in various breast cancer models indicating that GATA-3 has tumor suppressive properties in normal cells.
Development of successful HIV vaccine immunogens continues to be a major challenge. Although gp120 was identified as having significant potential as a vaccine immunogen, attempts to elicit broadly neutralizing antibodies using recombinant gp120 failed. The highly flexible gp120 may present numerous conformations to the humoral immune system that are not found on the viral spike.
Aberrant function of the WNT-b-catenin pathway is a common underlying cause of tumorigenesis. Despite the attractiveness of the WNT-b-catenin pathway as a therapeutic target, WNT dependent cell signaling is also crucial for normal tissue development, and is ubiquitous in all organs. As a result, WNT-b-catenin pathway inhibitors cause many side effects and fail to meet FDA safety standards. A more targeted approach is needed to develop safe and effective WNT signaling inhibitors.
KRAS and other Ras-family enzymes are an important component of over 30% of human cancers, however, no effective therapeutics targeting Ras or Ras-driven cancers are currently available. The production of Ras proteins in vitro is required for the identification and characterization of Ras targeting drugs. An important step in producing the Ras protein involves prenylation of the C-terminus of the protein via farnesyltransferase, a modification that does not occur in prokaryotic organisms. Previous attempts to generate properly processed Ras in eukaryotic cells has
The Surgery Branch of the National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to carry out genotypic as well as phenotypic analysis of the 888 mel cell line in order to better understand the nature of tumor cells that respond to therapy. In addition, this cell line can be used as a target of humoral or cell mediated immune responses as a part of studies characterizing the nature of immune responses directed against tumor cells.
The successful development of new cancer therapeutics requires reliable preclinical data that are obtained from mouse models for cancer. Human tumor xenografts, which require transplantation of human tumor cells into an immune compromised mouse, represent the current standard mouse model for cancer. Since the immune system plays an important role in tumor growth, progression and metastasis, the current standard mouse model is not ideal for accurate prediction of therapeutic effectiveness in patients.
Scientists at the NCI developed a research tool, a murine cell line model (JygMC(A)) with a reporter construct, of spontaneous metastatic mammary carcinoma that resembles the human breast cancer metastatic process in a triple negative mammary tumor. The assay is useful for screening compounds that specifically inhibit pathways involved in mammary carcinoma and can improve clinical management of of triple negative breast cancer that are greatly refractory to conventional chemo and radiotherapy.
The National Institute on Drug Abuse's Medications Discovery Research Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize 4-phenylpiperazine derivatives as dopamine D3 selective ligands.
The National Cancer Institute seeks parties interested in collaborative research to evaluate or commercialize a diagnostic tool that can identify new drugs that increase chromosome instability. Although chromosomal instability is generally thought of as a driver of tumor growth, a threshold level exists where CIN becomes a barrier to tumor growth and therefore can be exploited therapeutically.