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Several novel tropolone derivatives have been identified that inhibit HIV-1 RNase H function and have potential for anti-viral activity due to reduced cellular toxicity.  Inhibiting RNase H function is a potential treatment for many viral infections, since RNase H function is essential for viral replication for many pathogenic retroviruses such as HIV-1 and HIV-2.  Although many hydroxytropolone compounds are potent RNase H inhibitors biding at the enzymatic active site, they are limited as therapeutic candidates by their toxicity in mammalian cells.  The toxicity thought to

The chemokine receptor, CCR4 is a seven transmembrane G protein-coupled cell surface receptor molecule with selective expression on cells of the hematopoietic system. In adult T cell leukemia (ATL), the cell-surface expression of CCR4 on leukemic cells has been found to be nearly universal. Therefore, a CCR4-directed chimeric antigen receptor (CAR) -cell may provide an effective therapeutic against ATL.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children with approximately 3,250 new cases occurring per year in the United States. About 20% of cases are refractory to current treatment protocols and there is a desperate need for targeted therapies that do not result in adverse side effects such as cognitive impairment. 

The National Cancer Institute's Laboratory of Pathology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics targeting vasodialation.

Nitric oxide (NO) plays an important role as a major intrinsic vasodilator, and increases blood flow to tissues and organs. Disruption of this process leads to peripheral vascular disease, ischemic heart disease, stroke, vascular insufficiency associated with diabetes, and many more diseases that are significant.

Topoisomerase enzymes play an important role in cancer progression by controlling changes in DNA structure through catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle. Therefore, topoisomerases are important targets for cancer chemotherapy. Many topoisomerase 1 (TOP1) inhibitors such as camptothecin, rinotecan, and topotecan are widely used anti-cancer agents that work by stabilizing the TOP1-DNA cleavage complex.

Despite therapeutic advances, human immunodeficiency virus (HIV) is still a pervasive disease, with approximately 37 million people infected worldwide. Peptides have become popular therapeutic agents, as these proteins offer structural diversity for many different diseases. Several peptides were commercially developed as HIV therapeutics, demonstrating the high potential for peptides in treating HIV. 

Existing microsphere technologies are used as therapy for certain cancers. The therapy is by way of occlusion, when the microspheres are delivered into blood vessels that feed a tumor. The physical dimensions of the microspheres occlude the blood supply and thus, killing the tumor. Some microspheres have also been modified to bind protein, elute drugs, and reduce inflammatory reactions as part of the therapy. However, one technical short-coming of existing microsphere technology is a limited capability to be visualized in real-time.

Chimeric antigen receptors (CARs) combine an antibody-based binding domain (and single chain fragment variable region, scFv) with T cell receptor signaling domains (CD3 zeta with a costimulatory domain, typically CD28 or 41BB). When T cells express CARs, they are activated in a major histocompatibility complex- (MHC) independent manner to kill tumor cells expressing the target to which the scFv binds.  CAR T cells targeting the B cell antigen CD19 have resulted in remissions in 60-80% of patients with pre-B cell precursor acute lymphoblastic leukemia (BCP-ALL).

Adoptive cell therapy (ACT) is a breakthrough form of cancer immunotherapy that utilizes autologous, antitumor T cells to attack tumors through recognition of tumor-specific mutations, or neoantigens. A major hurdle in the development of ACT is the exhausted phenotype exhibited by many neoantigen-specific T cells, which limits their efficacy and prevents a sustained immune response. 

Advanced stage cancers are typically marked by metastases of the primary cancer to secondary sites such as lungs, liver, and bones. Such metastatic cancers result in strikingly low 5-year survival rates, underscoring the need for novel therapeutics. For example, bone metastasis of primary breast cancer has a 5-year survival rate of 13%, lung cancer only 1%. There is a need for targeted therapy options specific to metastases. One approach to targeting metastases is to reduce cancer cell migration and invasion.