Study Links ESCO2 Loss to PARP Inhibitor Sensitivity

NYU Langone researchers report that reduced ESCO2 levels make cancer cells more vulnerable to PARP inhibitors in preclinical models.

Updated on Nov. 6, 2026 in Cancer

Study Links ESCO2 Loss to PARP Inhibitor Sensitivity

Researchers at NYU Langone Health's Perlmutter Cancer Center published a study in Nature Cell Biology identifying ESCO2 as a determinant of cancer cell sensitivity to PARP inhibitors. Partial loss of ESCO2 increased sensitivity to these drugs in colorectal, ovarian, and lung cancer cells.

Why it matters

The findings point to a molecular feature that may help explain why some tumors respond to PARP inhibitors while others do not. Identifying such markers could eventually inform how these treatments are selected for patients.

The evidence comes from CRISPR screens and quantitative single-molecule imaging in cancer cell models rather than patient trials. The study reports increased G-quadruplexes at a small subset of replication sites in ESCO2-depleted cells, but clinical relevance remains unestablished.

The players

NYU Langone Health

NYU Langone Health is a major academic medical center in New York City that houses the Perlmutter Cancer Center, where the study was led.

Eli Rothenberg

Eli Rothenberg is a researcher at NYU Langone Health who co-led the study as a co-corresponding author and is working with clinicians to apply imaging approaches to patient-derived cancer cells.

Dipika Gupta

Dipika Gupta is a researcher at NYU Langone Health who served as a co-corresponding author on the study examining ESCO2 and PARP inhibitor sensitivity.

The details

Researchers found that ESCO2-depleted cells retained the homologous recombination response yet showed increased G-quadruplexes concentrated in repetitive pericentromeric regions. After PARP inhibition, these structures built up further, DNA synthesis declined, and damage increased near centromeres. The protective response depended on PARP1 activity and involved TIMELESS and DDX11.

- The article about the Nature Cell Biology study was published on November 6, 2026.

Health Landscape

PARP inhibitors were developed around the idea that tumors with defective homologous recombination, such as those with BRCA mutations, are especially vulnerable to them. This study adds a replication-stress mechanism involving ESCO2 that could complement existing biomarkers in preclinical work.

For patients, this research remains at the laboratory stage and does not change current treatment options. Its significance lies in future work that may help clinicians decide which patients are most likely to benefit from PARP inhibitors.

The takeaway

Biomarkers beyond BRCA status may eventually help match PARP inhibitors to the patients most likely to benefit. Readers should watch for follow-up clinical studies before expecting changes in care.