Analogues of Modafinil for treating sleep and attention disorders

Modafinil has attracted attention for the treatment of cognitive dysfunction in disorders such as attention-deficit/hyperactivity disorder (ADHD) as well as cocaine and methamphetamine dependence.  However, modafinil has relatively low affinity for binding to the dopamine transporter (DAT) to block dopamine reuptake, and is water-insoluble, thus requiring large doses to achieve pharmacological effects.

Target for Anti-Tumor Immune Responses

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. 

PARP Inhibitor and NO-Donor Dual Prodrugs as Anticancer Agents

Poly-ADP ribose polymerase-1 (PARP-1) is a critical enzyme involved in DNA repair.  The inhibition of PARP has emerged as a promising strategy in cancer therapy.  Numerous PARP inhibitors have been developed and advanced into clinical trials, both for use as single agents in specific patient populations and as combination therapies with various chemotherapeutics.  The induction of strand break damage to DNA, as has been demonstrated in cancer cells treated with O2-arylated diazeniumdiolates, coupled with inhibition of DNA repair by PARP inhibitors, represents a novel rational

Mouse Model for the Preclinical Study of Metastatic Disease

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.

Nanoparticles for the targeted treatment of infected cells

Current treatments for cancer and viral infection are limited remedies that often suppress cell or viral replication rather than eliminate diseased cells entirely from the body. A further limitation is that these therapies often compromise healthy cells as well, leaving problems of recurrence and side effects.

Researchers at developed a novel therapeutic nanoparticle (NP) system harboring therapeutic small siRNA that can significantly enhance effectiveness and specificity of treatments by killing diseased cells.

Chimeric Antigen Receptors (CARs) for Treating Lymphoma and Other Cancers

Chimeric antigen receptors (CARs) are hybrid proteins that consist of two major components: a targeting domain and a signaling domain.  The targeting domain allows T cells which express the CAR to selectively recognize and bind to diseased cells that express a particular protein.  Once the diseased cell is bound by the targeting domain of the CAR, the signaling domain of the CAR activates the T cell, thereby allowing it to kill the diseased cell.  This is a promising new therapeutic approach known as adoptive cell therapy (ACT).

Assay to Screen Anti-metastatic Drugs

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.