Mouse Protein Shows Promise in Epigenetic Approach to Target Solid Tumors

A study published in Nature Communications reveals that STELLA, a mouse protein, could potentially disrupt cancer-causing epigenetic changes in human colorectal cancer cells. Researchers from the Johns Hopkins Kimmel Cancer Center and the Chinese Academy of Sciences found that the mouse version of STELLA was more effective than its human counterpart in impairing tumor growth by disrupting a key epigenetic factor.

The team identified specific amino acids responsible for the difference in activity between mouse and human STELLA. This discovery led to the development of a novel drug strategy using these amino acids to treat colorectal cancer in cell lines and a mouse model.

Stephen Baylin, co-author of the study, emphasized the importance of this research: "For solid tumors—the major killers in cance —there is a tremendous unmet need to develop new approaches to therapeutically block DNA methylation abnormalities."

The study focused on targeting UHRF1, a protein highly expressed in many solid tumors that guides the addition of methyl groups to tumor suppressor genes. Mouse STELLA was found to bind tightly to UHRF1, effectively sequestering it.

Based on their findings, the researchers developed a lipid nanoparticle therapy to deliver the mouse STELLA peptide as mRNA to cells. This approach showed promising results in mice, activating tumor suppressor genes and inhibiting tumor growth.

The potential applications of this research extend beyond colorectal cancer, as UHRF1 is implicated in numerous cancer types.