Genomic instability is a core characteristic of cancer, often stemming from defects in DNA damage response (DDR) or increased replication stress. DDR defects can lead to significant genetic alterations, including changes in gene copy numbers, gene rearrangements, and mutations, which accumulate over time and drive the clonal evolution of cancer cells. However, these vulnerabilities also present opportunities for targeted therapies that exploit DDR deficiencies, potentially improving treatment efficacy and patient outcomes. The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality. This achievement has spurred further research into identifying additional therapeutic targets within the DDR pathway. Recent progress includes the development of inhibitors targeting other key DDR components such as DNA-PK, ATM, ATR, Chk1, Chk2, and Wee1 kinases. Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies.

Application of machine learning approaches to predict the 5-year survival status of patients with esophageal cancer Xian Gong, Bin Zheng, Guobing Xu, Hao Chen, Chun Chen

Thoracoscopic segmentectomy is the recommended treatment option for small peripheral pulmonary nodules. To assess the ability of preoperative 3D reconstruction CT to shorten the operative time and improve perioperative outcomes in thoracoscopic segmentectomy compared with standard chest CT, we conducted this randomized controlled trial. The DRIVATS study was a multicentre, randomized controlled trial conducted in three hospitals between July 2019 and November 2023. Patients with small peripheral pulmonary nodules not reaching segments borders were randomized in a 1:1 ratio to receive either 3D reconstruction CT or standard chest CT before thoracoscopic segmentectomy. The primary end-point was operative time. The secondary end-points included incidence of postoperative complications, intraoperative blood loss and operative accident event. A total of 191 patients were enrolled in this study: 95 in the 3D reconstruction CT group and 96 in the standard chest CT group. All patients underwent thoracoscopic segmentectomy except for one patient in the standard chest CT group who received a wedge resection. There is no significant difference in operative time between the 3D reconstruction CT group (median, 100 min [IQR, 85–120]) and the standard chest CT group (median, 100 min [IQR, 81–140]) (P = 0.82). Only one intraoperative complication occurred in the standard chest CT group. No significant difference was observed in the incidence of postoperative complications between the two groups (P = 0.52). Other perioperative outcomes were also similar. In patients with small peripheral pulmonary nodules not reaching segments borders, the use of 3D reconstruction CT in thoracoscopic segmentectomy was feasible, but it did not result in significant differences in operative time or perioperative outcomes compared to standard chest CT.