Nitric oxide (NO) has a broad spectrum of actions in physiological and pathological processes. NO-donor drugs have shown therapeutic effect in several cancer types by inducing apoptosis but the concentrations required have suggested limited clinical applicability. For cancers such as non-small cell lung cancer where most therapies are not curative, there remains a need for effective treatments.
A number of factors can play a detrimental role in the process of wound healing such as poor nutritional status, smoking, various drugs, cancer, and diabetes. Wound healing impairment is a challenging clinical problem with no efficacious treatments currently available. Nitric oxide (NO) has been shown to play a role in the process of wound healing by promoting both the proliferative and remodeling phases of healing.
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
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
Tumor necrosis factor receptor type 2 (TNFR2)-expressing regulatory T cells (Tregs), present in the tumor microenvironment, play an important role in tumor immune evasion. TNFR2 plays a crucial role in stimulating the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses. In addition to its expression on Tregs, TNFR2 is also known to be overexpressed on some types of tumors and the survival and growth of these tumor cells is promoted by ligands of TNFR2.
Immune checkpoint inhibitors (e.g. CTLA-4, PD-L1) have recently shown significant promise in the treatment of cancer. However, when used alone, these checkpoint inhibitors are limited by the absence or repression of immune cells within the targeted cancer. For those cancers associated with these limited immune systems, there remains a need for effective therapies. Agents capable of recruiting and activating immune cells to these types of cancers could extend the overall and complete response rates of combination therapies within the immunooncology domain.
HMGN polypeptides belong to the high mobility group (HMG) family of chromosomal binding peptides. HMGN polypeptides typically function inside the cell nucleus to bind to DNA and nucleosomes and regulate the transcription of various genes. HMGN polypeptides also can be released by peripheral blood mononuclear cells. However, the extracellular release of a HMGN polypeptide initiates activation of the immune system. Therefore, it has potential use as a biological therapeutic for stimulating an immune response.
Diazeniumdiolates comprise a diverse class of NO-releasing compounds and materials that are known to exhibit sufficient stability to be useful as therapeutics.
The National Cancer Institute’s Protein Expression Laboratory seeks parties to co-develop dual luminescent/fluorescent cancer biomarkers.
In research settings, visualization of tumors or tumor cells is often done using either bioluminescence or fluorescence. However, both of these methods have shortcomings: bioluminescence is not sensitive enough to sort individual tumor cells, and fluorescence cannot be used effectively to view internal tumors and is best used with surface tumors.
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.