Repositioning PARP inhibitors in the treatment of thoracic malignancies

Targeting genome integrity dysfunctions impedes metastatic potency in non–small cell lung cancer circulating tumor cell–derived explants

“…JCI Insight 2022;7(11):e155804 https://doi.org/10.1172/jci.insight.155804 HRD status. Others are currently evaluating PARPi activity with or without chemotherapy in NSCLC patients, harboring HRD or not (12). In a recent study assessing the occurrence of HR-related mutations across several cancers, HRD was reported in 5% of NSCLC patients and 2% of BRCA1/2 variants were pathogenic in this population (41).…”

“…JCI Insight 2022;7 (11):e155804 https://doi.org/10.1172/jci.insight.155804 breast, pancreas, and prostate) and are highly effective in potentiating chemotherapy, based on the biological rationale that the deficiency in DNA repair machinery modulates tumor response to platinum chemotherapy (7)(8)(9)(10). However, clinical studies assessing PARPi efficacy either in combination with chemotherapy or as maintenance treatment have failed to yield any significant benefit in chemosensitive NSCLC tumors with or without BRCA mutations (11,12).…”