ecDNA Amplifications in Cancer

The purpose of this meeting is to explore the formation and function of extrachromosomal DNA (ecDNA) amplifications in cancer. In recent years, driven largely by advances in genomics and DNA sequencing technologies, we have learned that extrachromosomal DNA is far more prevalent in tumors than previously appreciated. ecDNA is present in 20-40% of all human cancers and is particularly common in aggressive cancers notoriously difficult to treat, such as brain cancer. Moreover, our inability to effectively treat cancer is due to an innate ability of ecDNA cancers to evolve in response to environmental stressors. We have further come to learn that circular ecDNAs incorporate active gene enhancer elements that provide a selective growth advantage beyond that of the oncogene alone. This highlights an additional layer of regulatory complexity in canonical cancer driver events that will need to be considered to maximize targeted cancer therapies for patients. This Forbeck Forum seeks to unite investigators focused on ecDNA biology with experts in cancer genetics studying structural variation, epigenomics, and gene regulation. There are several key basic and translational questions that remain unresolved. What genetic processes drive ecDNA formation? What are the “rules” governing regulation of oncogenes on ecDNA? How does ecDNA impact cellular function? Can we use this knowledge to drug previously undruggable targets? We expect the open sharing of new ideas will facilitate collaborations designed to advance our fundamental understanding of how human cancers form and evolve, and how to potentially exploit this new understanding for precision oncology.

ecDNA is a red-hot topic. Industry has expressed a keen interest targeting cancers caused by ecDNA amplifications. The field is poised to make major advances that have translational implications for many cancer patients.

This meeting will be chaired by Peter Scacheri, PhD of Case Western Reserve University and Chia-lin Wei, PhD of The Jackson Laboratory of Genomic Medicine.

To learn more about this forum and it's participants, please visit forbeckforums.org.

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