An international collaboration of scientists has developed a novel compound, corin, that targets epigenetic modifying proteins in melanoma cells to inhibit their growth. The findings, published recently in Nature Communications, suggest corin could be used to treat patients without significant side effects.
Epigenetic modifications of a cell contribute to a tumor’s ability to grow uncontrollably, and also can enable tumors to become resistant to drugs and therapies. Genes within cells can be turned on or off by altering the accessibility of the DNA and the chromatin structure through DNA methylation and histone modification. Histone modification has been identified as a key feature in disease processes.
There are few epigenetic drugs currently in clinical use; histone deacetylase inhibitors are used to treat some lymphomas, and histone demethylase inhibitors to treat some leukemias. Corin is both a demethylase and deacetylase inhibitor, making it an attractive inhibitor of epigenetic modifications as it can more selectively target epigenetic compounds.
Co-corresponding author Rhoda Alani, the Herbert Mescon Chair of Dermatology at Boston University School of Medicine explained: "It is anticipated that this novel compound will have significant efficacy in human melanomas and other cancers either as a stand-alone therapy or in combination with other targeted or immune-based therapies."
The compound was first tested in vitro using a cell culture system, revealing cancer-associated processes to be effected such as cell growth, differentiation and migration. In an animal model for melanoma it was found to inhibit tumor cell growth, but not cause appreciable toxicities.
The research is also expected to influence the design of drugs for other diseases such as those mediated by the immune system. It is hoped that this research will pave the way for a new class of drugs.
"It is expected that this study will lay the foundation for developing a new class of potent and effective cancer therapies and the development of reagents targeting epigenetic events in immune-mediated diseases as well as other epigenetically-influenced diseases," concluded Alani.
Kalin JH, Wu M, Gomez AV et al. Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors. Nature Communications. 9(53) (2018); https://www.eurekalert.org/pub_releases/2018-01/buso-rcn010218.php