Chromatin Remodeler Offers New and Promising Target Against Prostate Cancer

New study reveals inhibiting SWI/SNF chromatin remodeling complex closes the door to pro-cancer transcription factors, preventing oncogene expression. Dovetail’s HiChIP technology played an essential role in this discovery.

SCOTTS VALLEY, Calif.--(BUSINESS WIRE)--Dovetail Genomics, the industry leader in advanced proximity ligation genomic solutions, today announced 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. 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.

“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: https://www.nature.com/articles/s41586-021-04246-z

About Dovetail Genomics

Dovetail Genomics LLC is transforming genomics by making long-range information readily accessible to all. The company enables researchers and clinicians to solve complex problems involving de novo assembly, structural variation, microbiome analysis, cancer research, phasing analysis and more by providing them a more comprehensive view of the genome. With 68 pending applications and 14 issued patents, its proprietary in vitro proximity ligation approach and assembly algorithms simplify genomic discovery by integrating the highest quality long-range genomic information with next-gen sequencing output. Dovetail is based in Scotts Valley, California. For more information on Dovetail, its technology, and service offerings, visit https://dovetailgenomics.com/omni-c/. Follow Dovetail on Twitter @DTGenomics.