Pharmacologic Reversal of Epigenetic Silencing of the Anticancer Protein BRM: A Novel Therapeutic Approach

Recent research published in the journal Oncogene has identified a novel targeted treatment strategy for cancer using pharmacologic reversal of epigenetic silencing of the anticancer protein BRM. The study, conducted by S. Gramling and colleagues at the University of Florida, found that compounds RH (RH02032) and GK (GK0037) could effectively restore BRM expression and function in cancer cells, inhibiting BRM-dependent growth across a wide range of cancer cell lines. This approach has the potential to provide a new therapeutic option for cancer treatment.

Key Takeaways:

• The authors identified 15-20% of solid tumor types where BRM is inactivated, making it a potential target for cancer treatment.
• A high-throughput drug screen identified compounds RH (RH02032) and GK (GK0037) as reactivating agents for BRM.
• Both compounds led to robust re-expression of BRM, induced downstream expression of BRM-dependent genes, and inhibited BRM-dependent growth across various cancer cell lines.
• The loss of BRM has been shown to be a reversible epigenetic change, rather than an irreversible genetic alteration.
• Pharmacologic reversal of epigenetic silencing of BRM is a potentially viable and novel therapeutic approach for cancer treatment.

Statistics:

• 15-20% of solid tumor types have BRM inactivated.
• 2 compounds, RH (RH02032) and GK (GK0037), were found to be effective reactivating agents for BRM.
• BRM-dependent growth was inhibited across a wide range of cancer cell lines.
• BRM is a key subunit of the SWI/SNF complex and a putative tumor suppressor gene.

Sources:

• S. Gramling et al., "Pharmacologic reversal of epigenetic silencing of the anticancer protein BRM: a novel targeted treatment strategy," Oncogene, 2011;30(29):3289-94.