Research Indicates Histone Protein Inhibition as Cancer Treatment

Sherif El-Refai

Sherif El-Refai focuses his work on experimental and clinical interventions. Sherif El-Refai currently works within the University of Kentucky’s Black lab, where researchers use gene expression to develop targeted cancer treatments.

In March 2017, researchers at Rockefeller University announced the development of an intervention that may reduce tumor growth by regulating gene expression. The research centers on proteins known as histones, changes to which may activate or deactivate a gene. Reader proteins within the cell then bind to the altered histone and facilitate activity of the gene.

Cancer researchers have already identified a type of reader protein known as the BET protein, which can inhibit tumor growth. The new discovery from the research team at Rockefeller University involves a type of protein that has similar potential to the BET protein but that shares a particular feature known as a YEATS domain. Like the BET protein, a protein with the YEATS domain binds to histones affected by a chemical mark known as an acetyl group.

Although the relevance of this particular functionality is as yet unknown, researchers do know that proteins with the YEATS domain may fuse with the MLL protein in certain patients with leukemia. Researchers tested this function by deleting a YEATS domain protein known as ENL from leukemia cells in mice, who had a significantly improved prognosis following the transplant of ENL-depleted proteins.

Researchers are now working on developing combination therapies that combine YEATS domain blockage with existing drugs that work as bromodomain inhibitors. The hope is to further explore the potential of YEATS domain blockers not only in leukemia but also in cancers of other types.


A New MicroRNA Therapy for Breast Cancer



Sherif El-Refai, PharmD, MBA, is currently pursuing further education as a doctoral student at the University of Kentucky. Focused on clinical and experimental therapeutics, Sherif El-Refai works within the university’s Black Lab, where researchers are investigating how manipulation of gene expression can affect cancer treatment outcomes.

Metastasis, the spread of cancer throughout the body, stands out as the most common cause of death in patients with breast cancer. Recently, however, researchers from the Massachusetts Institute of Technology’s (MIT’s) Institute for Medical Engineering and Science announced the development of a new therapy that may help to control this process. The methodology makes use of microRNA, a type of small noncoding ribonucleic acid (RNA) molecule that directs expression of a particular gene.

The research team began by analyzing a triad of datasets to identify the microRNA molecules active in breast cancer progression. Analysis uncovered a particular single nucleotide polymorphism (SNP), a kind of gene variant, that disrupts binding of microRNA molecules miR-96 and miR-182. This in turn prevented the microRNA’s in question from limiting expression the protein Palladin, known to be a factor in breast cancer metastasis.

Using this knowledge, researchers then created a method of delivering microRNA molecules to tumors in the breast. They placed engineered miR-96 and miR-182 into a nanoparticle, which they also infused with chemotherapy pharmaceutical cisplatin, and embedded the nanoparticle into a hydrogel carrier. When introduced to tumors in mice subjects, the treatment slowed tumor growth as well as metastasis.

The success of this experiment prepares the team to move on to the next phase of investigation. Lead scientist Dr. Natalie Artzi reports that the next step will be a larger mouse model, followed by clinical trials.