A study led by researchers at NYU Langone Health’s Perlmutter Cancer Center identifies specific DNA replication issues that affect how cancer cells respond to PARP inhibitors. The research, published in Nature Cell Biology, highlights the role of the ESCO2 protein in determining sensitivity to these drugs. The team found that even a partial loss of ESCO2 increased sensitivity in colorectal, ovarian, and lung cancer cells.
The researchers utilized CRISPR screens and quantitative single-molecule imaging to pinpoint replication-associated damage sites. They discovered that reduced ESCO2 levels led to an increase in G-quadruplexes, which obstruct DNA copying, particularly in repetitive regions near centromeres.
The findings suggest that location, rather than just the quantity of DNA damage, plays a crucial role in treatment response. The authors aim to develop biomarkers for cancer drug sensitivity and are working on applying these imaging techniques to patient-derived cancer cells.
Source: genengnews.com · Image: Central cancer research laboratories by Unknown photographer, Public domain, via Wikimedia Commons
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