The National Cancer Institute's Urologic Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of Tempol to target HIF-2a in cancer.
Diverse human cancers like colorectal, pancreatic, ovarian, melanoma, and pre-cancers express NADPH oxidases (NOX) at high levels. Reactive oxygen species (ROS) produced from metabolic reactions catalyzed by NOX in tumors are essential to the tumor’s growth. Though drugs that inhibit ROS production by NOX could be effective against a variety of human cancers, these types of drugs are not widely available.
Adoptive cell therapy (ACT) using tumor-specific T cells can produce positive clinical responses in some cancer patients. Nevertheless, several obstacles to the successful use of ACT for the treatment of cancer and other conditions remain. For example, one or more of the in vivo persistence, survival, and antitumor activity of tumor-specific T cells can, in some cases, decrease following adoptive transfer. Accordingly, there is a need for methods of obtaining a robust population of tumor-specific T cells for ACT.
Cytokines are a broad category of intercellular signaling proteins that are critical for intercellular communication in human health and disease. However, systematic profiling of cytokine signaling activities has remained challenging due to the short half-lives of cytokines, and the pleiotropic functions and redundancy of cytokine activities within specific cellular contexts.
Griffithsin is a potent anti-viral protein with activity against HIV, HCV, Sars, HSV 1 & 2 and other viruses. It is active against HIV and HCV at picomolar concentrations. Griffithsin is moving into clinical trials as an anti-HIV microbicide. Based on the structure of griffithsin and the necessities of pharmaceutical product development and regulatory approval, certain mutations in the sequence of griffithsin have been generated which could add to the stability and solubility of the protein.
Dopamine is a major neurotransmitter in the central nervous system and among other functions is directly related to the rewarding effects of drugs of abuse. Dopamine signaling is mediated by D1, D2, D3, D4 and D5 receptors. The dopamine D3 receptor is a known target to treat a variety of neuropsychiatric disorders, including substance use disorders (e.g. cocaine and opioid), schizophrenia and depression.
X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene.
Scientists at the NCI's Surgery Branch have developed anti-CD70 chimeric antigen receptors (CARs) to treat cancers. CD70 is an antigen that is expressed on a variety of human cancers such as renal cell carcinoma, glioblastoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. The anti-CD70 CARs are hybrid proteins consisting of a receptor portion that recognizes CD70 antigen, and intracellular T cell signaling domains selected to optimally activate the CAR expressing T cells.
Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is essential for regulating DNA damage checkpoints during the cell cycle. ATR, is phosphorylated at threonine 1989 site (T1989) in response to DNA damage and ATR activation leads to activation of downstream substrates, signaling cascades and cell cycle arrest. ATR is a potential target for anticancer therapeutics to induce cancer cell death by inhibiting cell cycle arrest pathways in response to chemotherapeutics.
Surgery is the standard care for patients with stage I lung cancer. Despite successful surgery, 20-30% of patients will relapse. Chemotherapy can improve patient survival; however, it is controversial if early stage cancer patients should be treated with chemotherapy since, for many cases, it will harm quality of life with little therapeutic benefit.