Cluster of differentiation 24 (CD24) is a small, highly glycosylated cell adhesion protein that is normally expressed by immune as well as epithelial, neural, and muscle cells. Tumor CD24 expression has been linked with alterations in several oncogenic signaling pathways. In addition, the CD24/Siglec-10 interaction has been implicated in tumor immune evasion, inhibiting macrophage-mediated phagocytosis as well as natural killer (NK) cell cytotoxicity. CD24 blockade has shown promising results in preclinical studies. Although there are limited data on efficacy, monoclonal antibodies against CD24 have demonstrated clinical safety and tolerability in two clinical trials. Other treatment modalities evaluated in the preclinical setting include antibody–drug conjugates and chimeric antigen receptor (CAR) T cell therapy. In this review, we summarize current evidence and future perspectives on CD24 as a potential target for cancer immunotherapy.

The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing a reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry, and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system, and their interplay and, therefore, potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.

Lung cancer is the leading cause of cancer-related mortality among both men and women worldwide, underscoring the need for an effective treatment strategy. For early-stage non-small cell lung cancer [NSCLC], surgical resection is the standard treatment. Robotic-assisted thoracic surgery [RATS] and video-assisted thoracic surgery [VATS] are better than open thoracotomy because they are less invasive. Recent lung cancer screening programs are detecting NSCLC at earlier stages, which is expected to result in an increase in the number of NSCLC surgeries as early-stage cases are diagnosed. A limited number of randomized controlled trials have compared RATS and VATS in operable NSCLC. We conducted a literature review to summarize the available evidence on these two surgical techniques. The purpose of this study is to compare the intraoperative and postoperative outcomes of RATS and VATS in early-stage NSCLC patients. RATS shows lower conversion rates to thoracotomy (6.3% vs. 13.1% p < 0.01) and more thorough lymph node dissection than VATS (e.g., 7.5 vs. 5.6 stations, p < 0.001). However, RATS is linked to considerably higher costs (USD 22,582 vs. USD 17,874, p < 0.05) and longer operative times (median 241.7 vs. 214.4 min, p = 0.06). The two techniques exhibited minimal differences in postoperative complications and pain, while RATS patients experienced shortened hospital stays (4–5 vs. 5–6 days, p < 0.006). While the accuracy of staging and treatment planning is improved by the improved lymph node retrieval in RATS, the long-term survival rate is still uncertain.

The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry and mitotic catastrophe. Recent data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system and their interplay and therefore potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.

Lung cancer (LC) is a serious health problem worldwide. Survival outcomes have improved over time due to the widespread use of novel therapeutic agents, including immune checkpoint inhibitors (ICIs). Endocrine immune-related adverse events (e-irAEs) are common in LC patients treated with ICIs. We performed a retrospective study of patients with LC who received treatment with ICIs at a tertiary referral center between January 2014 and October 2023. In total, 983 LC patients were included in the study. E-irAEs presented at a median time of 4.1 months and included hypothyroidism (15.6%), hyperthyroidism (4.3%), adrenal insufficiency (0.4%), hypophysitis (0.4%), and diabetes mellitus (0.2%). These toxicities were not related to the duration of treatment or the type of ICIs. Most (97.6%) e-irAEs were mild (grade 1–2). Median overall survival (OS) was higher in LC patients who experienced e-irAEs (31.6 months) compared to those who did not (10.8 months). The difference remained statistically significant in the 3-month (HR: 0.42) and 6-month landmark analysis (HR: 0.51). The OS advantage was observed in both patients with NSCLC (HR: 0.36) and SCLC (HR: 0.27). Additional research is needed to validate the role of e-irAEs as an independent predictor of survival outcomes in patients with LC.