Investigators at the National Institutes of Health (NIH) have discovered compounds that have potential as novel anti-androgen therapeutics. The immunophilin protein FKBP52 is part of a protein complex that helps fold the androgen receptor (AR) protein, a target for treating prostate cancer, and enhances its activity. Disruption of the FKPB52-AR interaction greatly reduces the activity of the AR.

Clinically known as Neuronal Ceroid-Lipofuscinoses (NCL), Batten disease, is a rare neuron killing disease and one of the lysosomal storage disorders (LSDs).  It is associated with a mutation or lack of palmitoyl-protein thioesterase-1 (PPT1) gene. It manifests very early in a child's life causing absence of brain activity as early as 4 years of age.

Adoptive cell therapy (ACT) using genetically engineered T-cell receptors (TCRs) is a promising cancer treatment. These TCRs target genetic mutations unique to patients and play an important role in tumor regression. However, mutation-reactive T-cells and their TCRs can be difficult to identify and isolate from patients. Therefore, we need more efficient methods of isolating mutation-reactive T-cells for use with ACT. 

Hypoxia is a characteristic of many solid tumors resulting from accelerated cellular proliferation and inadequate vascularization. HIF-1 is a transcription factor critical for maintaining cellular homeostasis in, and adaptively responding to, low oxygen environments. HIF-1 becomes activated through binding to the transcriptional co-activator protein p300. Disruption of the HIF-1/p300 interaction could potentially modulate HIF-1 activity.

Diazeniumdiolates comprise a diverse class of NO-releasing compounds and materials that are known to exhibit sufficient stability to be useful as therapeutics.

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.

The National Cancer Institute Laboratory of Molecular Biology seeks parties for collaborative research to co-develop and commercialize antibody drug/toxin conjugates as liver cancer therapy and diagnostics. 

Despite recent breakthroughs in cancer immunotherapy, T-cell based therapies achieve limited efficacy in solid tumors. Immunosuppression, antigen escape and physical barriers to entry into solid tumors are issues faced. Identifying regulators in T-cell dysfunction remains challenging due to limitations of current screening platforms. 

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths in developed countries.  Despite the availability of several synergistic, targeted therapy regiments, the 5-year survival rate for NSCLC is only 15%.  The poor prognosis of NSCLS is due in part to limitations of current treatments, which do not trigger an immune response against NSCLC, nor can they be directly delivered into the lungs.  

• Topoisomerase 3B (TOP3B) is the only topoisomerase that can act on RNA as well as DNA. Thus, it is a target of interest for the development of cancer therapies and RNA viral infection therapies. TOP3B is not an essential gene for carcinogenesis, but a subset of cancer cells with pre-existing genome instability are particularly vulnerable to the inactivation of TOP3B. While inhibitors for other topoisomerases are among the most potent and widely used anticancer agents, there are no known inhibitors of TOP3B.