Elizabeth Brunk, MSc, PhD
Controlling Rapid and Reversible DNA Adaptations Through Epigenetic Drugs
Abstract
Traditional drug discovery efforts predominantly target rapid, reversible protein-mediated adaptations, aiming to disrupt cancer cells’ ability to withstand therapeutic pressures. However, cancer cells employ additional strategies, including changes in DNA. DNA adaptations are perceived as slow, irreversible, and unpredictable alterations, such as point mutations or the selection of drug-resistant clones. Rarely do we consider that DNA changes can be rapid, reversible, and predictable—yet this is the case with extrachromosomal DNA (ecDNA). This project pioneers a novel strategy to target these adaptations, integrating Artificial Intelligence (AI) with single cell imaging and multi-omics sequencing to analyze ecDNA’s influence on drug response. By focusing on epigenetic remodeling drugs, we aim to block ecDNA-mediated adaptation, thereby guiding new therapeutic strategies and offering a forward-thinking approach that aligns with PhRMA’s drug discovery goals.
Winning the Foundation award enables our systems genomics lab, which integrates single-cell technologies and AI, to pursue rapid DNA adaptations in cancer. This support allows us to target and prevent these changes, improving patient responses and advancing durable treatments.
