RNA nanoparticles have the potential to serve as excellent drug or imaging delivery systems due to their designability and versatility. Furthermore, the RNA nanoparticles of the invention are also capable of self-assembly and potentially form nanotubes of various shapes which offer potentially broad uses in medical implants, gene therapy, nanocircuits, scaffolds and medical testing.
Cancer stem cells are a minority population of cells in tumors that initiate and sustain the cancer and which are resistant to therapy; they may cause tumors to recur after curative treatment. Current therapies generally do not target cancer stem cells.
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.
RNA interference (RNAi) is a naturally occurring cellular post-transcriptional gene regulation process that utilizes small double-stranded RNAs to trigger and guide gene silencing. By introducing synthetic RNA duplexes called small-interfering RNAs (siRNAs), we can harness the RNAi machinery for therapeutic gene control and the treatment of various diseases.
Antibody drug conjugates (ADC) can demonstrate high efficacy as cancer therapeutics, however, much more can be done to improve their efficacy and safety profile. Site-specific antibody drug conjugation is a promising way to do this. Scientists at the NCI’s Laboratory of Experimental Immunology have identified a fully human monoclonal antibody, m860, that binds to cell surface-associated Her2 with affinity comparable to that of Trastuzumab (Herceptin) but to a different epitope.
Adoptive immunotherapy is a promising new approach to cancer treatment that engineers an individual''s innate and adaptive immune system to fight against specific diseases, including cancer with fewer side-effects and more specific anti-tumor activity in individual patients. T cell receptors (TCRs) and Chimeric Antigen Receptors (CARs) are proteins that recognize antigens in the context of infected or transformed cells and activate T cells to mediate an immune response to destroy abnormal cells.
Several malignancies associated with a poor prognosis such as lung, pancreatic and colorectal cancers frequently harbor constitutively active KRAS mutants, which play a pivotal role in oncogenesis. Currently, there are no potentially curative treatments against most mutant KRAS harboring cancers once they become metastatic and unresectable. Despite intensive efforts to develop potent mutant KRAS inhibitors, none have shown a significant improvement to patients.
The MUC-1 tumor associated antigen has been shown to be overexpressed and/or underglycosylated in a wide range of human cancers. The C-terminus region of MUC-1 (MUC-1C) has been shown to be an oncogene and has been associated with a more aggressive phenotype in several different cancers.
One major challenge in the development of effective cancer therapies is a lack of universal, cancer specific markers in target cells. The current standard therapies rely on surgery, chemotherapy, and radiation therapy. Such procedures lead to a population of resistant cancer cells that makes further applications of chemotherapy/radiation therapy ineffective. Additionally, the systemic application of chemotherapy lacks specificity and has off-target systemic effects that lead to adverse side effects.