On December 22, 2021 Dovetail Genomics, the industry leader in advanced proximity ligation genomic solutions, reported details of a new study, led by University of Michigan researchers and published in Nature, which showed for the first time that inhibiting the SWI/SNF chromatin remodeling complex prevents several oncogenes from being expressed and slows prostate cancer growth in cell and animal models (Press release, Dovetail Genomics, DEC 22, 2021, View Source [SID1234597627]). These findings were made possible, in part, by Hi-C technology developed by Dovetail Genomics, with the company’s proximity ligation HiChIP MNase Kit providing essential information about 3D chromatin architecture, illuminating the effect the PROTAC had on chromatin remodeling. In addition, Dovetail scientists Mital Bhakta and Jay Ghurye contributed to the paper.
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"This is a revolutionary finding," said Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and senior author on the paper. "By controlling chromatin structure in prostate cancer cells, we shut down several oncogenic pathways at once. This could offer new hope for patients, particularly those with resistant disease."
Chromatin is the combination of DNA, RNA and proteins that tightly package genetic material in the nucleus. Cells have evolved complex mechanisms, including the SWI/SNF complex, to open up chromatin and allow gene expression.
In the study, the research team designed a proteolysis targeting chimera (PROTAC), a small molecule compound, that degrades SMARCA2 and SMARCA4, essential SWI/SNF components. This degradation had a ripple effect. Inhibiting SWI/SNF kept chromatin closed to cancer-driving transcription factors, which could not reach gene enhancers, muting well-known oncogenes, such as AR (androgen receptor), FOXA1, ERG and MYC.
This work highlights potential therapeutic targets to defeat enhancer-addicted prostate and possibly other cancers. Equally important, PROTAC synergized with the androgen receptor antagonists, which are often used to treat prostate cancer, making them more effective.
"Dovetail has always put an acute focus on cancer research, understanding that proximity ligation takes oncology studies to the next level," said Todd Dickinson, CEO of Dovetail Genomics. "We were thrilled to partner with Dr. Chinnaiyan on this study, helping to identify a critical advance in cancer data and research."
The full article can be found here: View Source