Internal medicine

DNA damage

Genome instability

Topotecan

Biology

Topoisomerase

Oncology

Immunology

Chemotherapy

Cancer research

Genetics

Medicine

Cancer Cell

Thomas et al. identify DNA replication stress as a therapeutic vulnerability of small cell neuroendocrine cancers (SCNCs). SCNCs with high neuroendocrine differentiation and enhanced replication stress are more likely to respond to ATR and topoisomerase I inhibition, which yielded durable tumor regressions in patients with platinum-resistant tumors.

Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress