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Primary liver tumors and secondary hepatic malignancies are among the leading causes of cancer-related deaths. Liver metastases account for 95% of all hepatic cancers, and the liver is the most common site for organ metastasis in the body. The gut microbiome serves an important role in antitumor immunity regulating the efficacy of chemo- and immunotherapies. The liver is exposed to gut bacteria through blood from the intestine, with 70% of the whole liver’s blood supply coming from intestinal blood. Changes in the commensal microbiome may affect immune cell function in the liver.

Epidermal growth factor receptor (EGFR) is a transmembrane protein involved in cell growth and proliferation. Mutations in this protein can lead to overexpression, causing several types of cancer; notably, non-small cell lung cancer (NSCLC). For example, mutations in EGFR are found in up to 50% of NSCLC patients and the E746-A750 deletion accounts for 30-40% of such EGFR mutations. Currently, there are no available therapeutics that specifically target the E746-A750 deletion. 

Human papillomavirus (HPV) has been associated with the cause of several cancer types, including cervical, anal, and head and neck cancers. There has been great success in preventing HPV infections with the development of prophylactic HPV vaccines, Gardasil and Cervarix. However, these vaccines have only been shown to prevent HPV infection and not treat those already infected with HPV. These vaccines elicit antibody responses to late HPV genes, and thus would not be effective in treating established tumors.

Several Fibroblast Growth Factor Receptor 4 (FGFR4) specific antibodies with binding affinity at the nanomolar range have been successfully developed at the Genetics Branch. These antibodies have been made into different formats of therapeutic including Antibody Drug Conjugate (ADC), Bispecific T cell engager (BiTE) ae well as Chimeric Antigen Receptor (CAR)-T cells.

Proof of principle experiments have shown that when treated with FGFR4 positive tumor cells:  

A significant challenge in developing therapies for the treatment and prevention of cancer has been the discovery, selection, and exploitation of antigens.

Scientists at the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD) have developed a method implemented as pulse sequences and software to be used with magnetic resonance imaging (MRI) scanners and systems. This technology is available for licensing and commercial development. The method allows for measuring and mapping features of the bulk or average apparent diffusion coefficient (ADC) of water in tissue – aiding in stroke diagnosis and cancer therapy assessment.

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.

Medical imaging is an important resource for early diagnostic, detection, and effective treatment of cancers. However, the screening and review processes for radiologists have been shown to overlook a certain percentage of potentially cancerous image features. Such review errors may result in misdiagnosis and failure to identify tumors. These errors result from human fallibility, fatigue, and from the complexity of visual search required.

T cells currently employed for T cell-based immunotherapies are often senescent, terminally differentiated cells with poor proliferative and survival capacity. Recently, however, scientists at the National Cancer Institute (NCI) identified and characterized a new human memory T cell population with stem cell-like properties. Since these T cells have limited quantities in vivo, the scientists have developed methods by which high numbers of these cells can be generated ex vivo for use in T cell-based immunotherapies.

Small molecule fluorescent probes are important tools in diagnostic medicine. Existing far-red and near-IR cyanine fluorophores (e.g. Cy5, Alexa 647, Cy7, ICG) are active in the far-red and near-range, but these agents suffer from modest quantum yields (brightness) which limit wide utility. It has been reported that the limited brightness of these fluorophores is due to an excited-state C-C rotation pathway.