Background: Recent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma. Methods: Two hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated. Results: There were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3–4 toxicities between groups (p = 0.445). Conclusions: Adjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

Background: The most common form of therapy for nonsmall cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. The authors aimed to quantify the risks of SPM associated with PORT treatment for young‑onset NSCLC in early stage. Methods: The authors screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology, and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray’s competing risk regression analysis was used to calculate the cumulative incidence of SPMs. Results: Among the 30 308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies [relative risks (RR)=1.31; 95% CI: 1.17–1.46], lung cancer (RR=1.23; 95% CI: 1.07–1.42), breast cancer (RR=1.74; 95% CI: 1.16–2.74), and colon and rectum cancers (RR=1.37; 95% CI: 1.07–2.06) as well as a negligible risk of second hematologic malignancies (RR=1.15; 95% CI: 0.82–1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60–69 years (RR=1.33), in white race (RR=1.36), diagnosed in 1975–2000 (RR=1.23) and 2001–2015 (RR=1.40), or diagnosed with lung adenocarcinoma (RR=1.55). Conclusion: PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer, as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients.

In the article titled “XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer” [1], there were errors in the reported sequences. It was raised to our attention [2] that the article includes mistargeted primer sequences as follows:

The progression of lung adenocarcinoma (LUAD) involves multiple molecular determinants, among which Oxysterol-binding protein-like 3 (OSBPL3) has been suggested to contribute to tumorigenesis, though its functional significance in LUAD remains poorly characterized. In this study, we elucidate the oncogenic functions and underlying mechanisms of OSBPL3 in LUAD pathogenesis. Analysis of clinical specimens revealed upregulated OSBPL3 expression in LUAD, which correlated with unfavorable patient outcomes. Genetic depletion of OSBPL3 in vitro impeded cellular proliferation, migratory capacity, and cell cycle progression, while inducing apoptotic cell death. Mechanistically, OSBPL3 was found to interact with the transcription factor NFE2L2, promoting its nuclear translocation and enhancing the transcriptional activation of PLAU, a downstream target gene. Upregulation of PLAU subsequently stimulated expression of key glycolytic enzymes through PI3K/AKT pathway activation, resulting in increased glucose consumption and lactate secretion. This metabolic reprogramming toward aerobic glycolysis facilitated malignant progression. Both genetic inhibition of PLAU and pharmacological blockade of AKT signaling abrogated the tumor-promoting phenotypes induced by OSBPL3. In vivo, OSBPL3 silencing significantly attenuated tumor growth and promoted apoptosis. Collectively, these findings identify an OSBPL3-NFE2L2-PLAU-AKT signaling axis that drives glycolytic metabolism and LUAD progression, showing its potential as a therapeutic target.

Non-small cell lung cancer (NSCLC) poses a formidable therapeutic challenge due to drug resistance and limited treatment efficacy. To address this, we developed a novel nanodrug delivery system, SPIO@SiO₂-ANB, which integrates superparamagnetic iron oxide nanoparticles (SPIOs), a silica (SiO₂) shell, and the surface-loaded multi-target tyrosine kinase inhibitor anlotinib (ANB). This platform enhances drug stability, enables tumor-targeted delivery, and induces ferroptosis. The synthesized nanoparticles demonstrated a monodisperse spherical morphology, pH-responsive ANB release, and efficient cellular internalization. In vitro, SPIO@SiO₂-ANB exhibited superior cytotoxicity against A549 and H460 NSCLC cells compared to free ANB, concurrently elevating intracellular reactive oxygen species (ROS) and modulating key ferroptosis-related proteins (COX-2, xCT, GPX4). In vivo studies using xenograft models revealed improved tumor accumulation and retention of SPIO@SiO₂-ANB, leading to significant tumor growth inhibition, enhanced apoptosis, and suppressed angiogenesis. This work presents a synergistic therapeutic strategy that combines ferroptosis induction with targeted therapy, offering a promising avenue for the safe and effective treatment of NSCLC.