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Advanced imaging uncovers genomic Achilles' heel that makes cancer cells vulnerable

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Advanced imaging uncovers genomic Achilles' heel that makes cancer cells vulnerable

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A small subset of vulnerable DNA sites can make cancer cells highly sensitive to targeted drugs called PARP inhibitors, a new study shows. Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, the work revolved around failures of DNA to copy itself at certain sites in genetic chains, which it must do for cells to divide and multiply as part of healing and growth. Cancerous cells depend on protective mechanisms that have evolved to overcome these failures when they are triggered by cancer drugs.

Published online in Nature Cell Biology, the study reveals how DNA replication failures at critical sites in chromosomes, the protein superstructures that house and provide access to DNA, determine how vulnerable cancer cells are to PARP inhibitors.

The research team pinpointed replication problems at critical chromosome regions and identified the protective response that keeps DNA replication failures in check. Blocking that protective response let localized damage caused by cancer treatments build up, compromising the cancer cells' survival.

The discovery reveals how the location of DNA damage can shape treatment response and provides a foundation for developing new biomarkers of cancer drug sensitivity.

, a professor in the Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine.



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