Immune checkpoint inhibitors (ICIs) have shown definite therapeutic effects in various types of cancers, especially non-small cell lung cancer (NSCLC). However, ICIs have unique side effects, called immune-related adverse events (irAEs), which can occur in various systems throughout the body. Among such irAEs, immune checkpoint inhibitor-related pneumonitis (ICI-P) is a fatal adverse reaction. In this review, we discussed the risk factors, pathogenesis, clinical characteristics, radiological manifestations, pathological features, diagnosis, grading, and management of ICI-P in NSCLC and the relationship between ICI-P and the efficacy of ICI therapy. In addition, we discussed the predictive factors for ICI-P. This review will play a crucial role in the prediction, evaluation, and management of ICI-P for widespread application of immunotherapy.

Purpose: While observational studies have identified obesity as a potential risk factor for gastric cancer, the causality remains uncertain. This study aimed to evaluate the causal relationship between obesity and gastric cancer and identify the shared molecular signatures linking obesity to gastric cancer.Methods: A two-sample Mendelian randomization (MR) analysis was conducted using the GWAS data of body fat percentage (exposure, n = 331,117) and gastric cancer (outcome, n = 202,308). Bioinformatics and meta-analysis of multi-omics data were performed to identify key molecules mediating the causality. The meta-analysis of the plasma/serum proteome included 1,662 obese and 3,153 gastric cancer patients. Obesity and gastric cancer-associated genes were identified using seven common gene ontology databases. The transcriptomic data were obtained from TCGA and GEO databases. The Bioinformatic findings were clinically validated in plasma from 220 obese and 400 gastric cancer patients across two hospitals. Finally, structural-based virtual screening (SBVS) was performed to explore the potential FDA-approved drugs targeting the identified mediating molecules.Results: The MR analysis revealed a significant causal association between obesity and gastric cancer (IVW, OR = 1.37, 95% CI:1.12-1.69, P = 0.0028), without pleiotropy or heterogeneity. Bioinformatic and meta-analysis of multi-omics data revealed shared TNF, PI3K-AKT, and cytokine signaling dysregulation, with significant upregulation of AKT1, IL-6, and TNF. The clinical study confirmed widespread upregulation of systemic inflammatory markers in the plasma of both diseases. SBVS identified six novel potent AKT1 inhibitors, including the dietary supplement adenosine, representing a potentially preventive drug with low toxicity.Conclusion: Obesity causally increases gastric cancer, likely mediated by persistent AKT1/IL-6/TNF upregulation. As a potential AKT1 inhibitor, adenosine may mitigate the obesity-to-gastric cancer transition. These findings could inform preventive drug development to reduce gastric cancer risk in obesity.

Brain metastasis from lung cancer is a prevalent mode of treatment failure associated with a poor prognosis. The incidence of brain metastasis has recently shown a dramatic increase. The early detection and risk stratification of lung cancer–related brain metastasis would be highly advantageous for patients. However, our current knowledge and comprehension of the underlying mechanisms driving brain metastasis in lung cancer pose significant challenges. This review summarizes the mechanisms underlying brain metastasis, focusing on the intricate interplay between lung cancer–derived tumor cells and the unique characteristics of the brain, recent advancements in the identification of driver genes, concomitant genes, epigenetic features, including miRNAs and long noncoding RNAs, as well as the molecular characterization of brain metastasis originating from other organs, which may further enhance risk stratification and facilitate precise treatment strategies.

Background and objective: Small cell lung cancer (SCLC) is the most aggressive type of lung carcinoma with high metastatic potential and chemoresistance upon relapse. Cancer cells remodel the existing metabolic pathways for their benefits and the perturbations in cellular metabolism are the hallmark of cancer. However, the extent of these changes remains largely unknown for SCLC. Materials and methods: We characterized the metabolic perturbations in SCLC cells (SCLCC) by metabolomics. Large-scale correlation analysis was performed between metabolites. Targeted proteomics and gene expression analysis were employed to investigate the changes of key enzymes and genes in the disturbed pathways. Results: We found dramatic decrease of metabolite–metabolite correlations in SCLCC compared with normal control cells and non-small cell lung cancer cells. Pathway analysis revealed that the loss of correlations was associated with the alternations of fatty acid oxidation, urea cycle, and purine salvage pathway in SCLCC. Targeted proteomics and gene expression analysis confirmed significant changes of the expression for the key enzymes and genes in the pathways in SCLCC including the upregulation of carbamoyl phosphate synthase 1 (urea cycle) and carnitine palmitoyltransferase 1A (fatty acid oxidation), and the downregulation of hypoxanthine–guanine phosphoribosyltransferase and adenine phosphoribosyltransferase in purine salvage pathway. Conclusion: We demonstrated the loss of metabolite–metabolite correlations in SCLCC associated with the upregulation of fatty acid oxidation and urea cycle and the downregulation of purine salvage pathways. Our findings provide insights into the metabolic reprogramming in SCLCC and highlight the potential therapeutic targets for the treatment of SCLC.

Background: Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates.Methods: We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6‐month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort).Results: Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression‐free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3‐ and 5‐year rates of 50.9% and 35.9%, respectively.Conclusion: DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra‐pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3‐year and 5‐year OS rates.