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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.

Due to the large degree of homology among dopamine D2-like receptors, discovering ligands capable of discriminating between the D2, D3, and D4 receptor subtypes remains a significant challenge. The development of subtype-selective pharmaceutical small molecules to activate (agonists) signals regulated by D2-like receptors has been especially difficult. 

Chemotherapy resistance in a wide array of cancers is often associated with enhanced glucose uptake and dysregulation of the insulin signaling pathway.  Therapeutics capable of inhibiting insulin signaling would be valuable as a stand-alone treatment and for sensitizing resistant tumors to standard chemotherapy regiments.  Researchers at NCI’s Genitourinary Malignancies Branch have synthesized and developed a series of Englerin-A ana

The Hippo signaling pathway regulates a multitude of biological processes including cell proliferation, apoptosis, differentiation, tissue homeostasis, and stem cell functions. This axis has been recently listed as one of the top 10 signaling pathways altered in human cancer. Its role in modulating cell growth and proliferation is mediated by the activation of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding domain (TAZ).

The Zbtb7b gene encodes the zinc finger transcription factor ThPOK (also known as cKrox) that promotes CD4 lineage differentiation in immature T cells. CD4+ T cells, also known as “helper” T cells, are critical for long-term immunity against pathogens as well as for promoting CD8+ “effector” T cell and effective B cell responses. ThPOK is needed for the development and functional fitness of CD4+ T cells as well as multiple aspects of the immune response to infection. As such, ThPOK offers a potential target for immune regulation.

Human immunodeficiency virus (HIV) remains a major global health challenge despite the advancement made in development of effective antiretrovirals (ARVs). ARVs are effective at limiting replication and spread of the virus, and progression to acquired immuno-deficiency syndrome (AIDS). However, ARVs often lead to emergence of drug-resistant virus strains insensitive to treatment and with toxic effects following long-term usage.

Researchers at the National Cancer Institute (NCI) have developed a new method of improving the efficacy of vaccines in patients with human immunodeficiency virus (HIV) by activating Ras. This method can be used to develop more efficacious vaccine compositions by activating Ras before, during, or after vaccination. Additionally, the researchers discovered that modulation of the Ras pathways could be a predictive biomarker of protection against HIV.

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.

Researchers at the Vaccine Research Center (“VRC”) of the National Institute of Allergy and Infectious Diseases (“NAID”) continue to pursue a safe and effective HIV-1 vaccine to combat the HIV-1/AIDS pandemic.

This technology includes a vaccine for lowering plasma triglycerides by inducing the formation of autoantibodies against either ANGPTL3 or ANGPTL4, which are inhibitors of Lipoprotein Lipase. This was done by conjugating synthetic peptides based on ANGPTL3 or ANGPTL4 to virus- like particles (VLPS). Injection of the vaccine in animal models was shown to induce the autoantibody against the target and to lower plasma triglycerides.