DNA Repair Deficiency and Therapeutic Vulnerability Across Solid Tumors: Insights from Thoracic Cancers

DNA repair pathways safeguard genomic integrity, and their dysfunction is a defining feature of many solid tumors. Deficiencies in homologous recombination, mismatch repair, base excision repair, and related pathways not only drive genomic instability and tumorigenesis but also create exploitable therapeutic vulnerabilities — as demonstrated by the success of PARP inhibitors in BRCA-mutant cancers. While these principles were first established in breast and ovarian malignancies, thoracic cancers, including non-small cell and small cell lung cancer, mesothelioma, and thymic tumors, present distinct and underexplored patterns of DNA repair deficiency, with important implications for treatment stratification and resistance mechanisms.This Research Topic aims to bring together current understanding of DNA repair deficiency across solid tumors, with a particular focus on the insights emerging from thoracic malignancies. We welcome contributions examining the molecular characterization of DNA repair pathway alterations, biomarkers predictive of response to DNA damage response (DDR)-targeted therapies, mechanisms of acquired and intrinsic resistance, and the translational potential of combining DDR inhibitors with immunotherapy, chemotherapy, or radiotherapy. Comparative analyses that connect findings in thoracic cancers to broader trends across solid tumor types are especially encouraged.By consolidating research on DNA repair deficiency and its therapeutic exploitation, this collection seeks to advance precision oncology approaches and highlight thoracic cancers as an informative model for understanding DDR biology more broadly. Topic editors: Francesca Iommelli, Caterina De Rosa, Viviana De Rosa Source: https://www.frontiersin.org/research-topics/84815/dna-repair-deficiency-and-therapeutic-vulnerability-across-solid-tumors-insights-from-thoracic-cancers