Cell Lung Cancer Research Articles

Targeting PRMT1 reduces cancer persistence and tumor relapse in EGFR- and KRAS-mutant lung cancer.

Incomplete killing of cancer cells undermines oncogene-targeting therapies and drives disease relapse. Eliminating cancer cells that persist during treatment is crucial for improving treatment outcomes. Here, we discovered that a specific isoform of type I protein arginine methyltransferases (PRMTs), namely PRMT1, enables lung cancer cells with EGFR or KRASG12C driver mutations and high STAT1 activity to persist through targeted drug treatments. PRMT1 knockdown, combined with EGFR or KRASG12C inhibitors, decreased persistence and delayed cancer cell regrowth across cell line models and significantly prolonged tumor regression in xenograft models. In contrast, we found that knockdown of two other type I PRMT isoforms, PRMT4 and PRMT6, increased persistence. Finally, we found that targeting PRMT1 to reduce persistence is more effective in lung cancer models with intact vs. deleted chromosome 5q31.1, a region enriched with JAK-STAT pathway genes, suggesting a potential stratification criterion. Together, our study pinpoints the PRMT1 isoform as a critical vulnerability of cancer persistence in EGFR- or KRASG12C-targeted therapies.

Developing Multiple Media Approach to Investigate Reproducible Characteristic VOCs of Lung Cancer Cells.

Cellular volatile organic compound (VOC) detection is crucial for studying lung cancer biomarkers. However, the reported VOC biomarkers from the same cell line seem to be inconsistent across different research groups. It is possibly related to the variation in culture media, and the result obtained by a conventional single medium approach (SMA) depends on what medium is used in the cell experiment. This study proposes a multiple media approach (MMA) to investigate reproducible characteristic VOCs of lung cancer cells. Using solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) in combination with untargeted analysis, we conducted two independently repetitive experiments to compare lung cancer cells (A549) and normal lung cells (BEAS-2B) under three culture media conditions (RPMI 1640, DMEM, and Ham's F12). Both experiments indicated that, compared with 62-96 VOCs obtained by the SMA, only two VOCs (3-methyl-1-butanol and 2-methyl-1-butanol) were reproducibly achieved by the MMA. Moreover, their concentrations were significantly lower in lung cancer cells than in normal cells. Further targeted analysis confirmed the downregulation trend of both VOCs in subcutaneous and primary tumor tissues from the lung cancer model mouse. The present work demonstrated that the MMA cell experiment, just like the multicenter trials for cell lines, can facilitate the discovery of reproducible characteristic VOCs. This provides a cellular experimental basis and scientific evidence for lung cancer biomarker investigation and even breath biopsy technique development.

MACC1 ablation suppresses the dedifferentiation process of non-CSCs in lung cancer through stabilizing KLF4

Metastasis-associated in colon cancer-1 (MACC1) was identified as a new player in lung cancer development, and some stemness-related genes can be novel transcriptional targets of MACC1. Cancer stem cells (CSCs) are responsible for sustaining tumorigenesis and plasticity. Both CSCs and non-CSCs are plastic and capable of undergoing phenotypic transition, especially the dedifferentiation of non-CSCs switch to CSC-like cells. However, the precise role of MACC1 during this process is largely unknown. Here, we showed that MACC1 promoted the transition from non-CSC to CSC in lung cancer. We found MACC1 was overexpressed in stemness enriched cells, enhancing the transition from no-CSCs to CSCs, while short-hairpin RNA-mediated Knockdown of MACC1 impaired this process. High-throughput sequencing and tumor specimen analysis revealed that MACC1 was negative correlated with Krüppel-like factor 4 (KLF4) expression level, which acts as a negative stemness regulator in lung cancer. Mechanistically, MACC1 delays the degradation of KLF4 mRNA by repressing the expression of microRNA-25, thereby promoting the KLF4 mRNA stabilization at the post-transcriptional level. Collectively, our findings may facilitate efforts to promote the development of precision targeted therapy for cancer stem cells in lung cancer.

PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma

BackgroundThe efficacy of tyrosine kinase inhibitors (TKIs) targeting the EGFR is limited due to the persistence of drug-tolerant cell populations, leading to therapy resistance. Non-genetic mechanisms, such as metabolic rewiring, play a significant role in driving lung cancer cells into the drug-tolerant state, allowing them to persist under continuous drug treatment.MethodsOur study employed a comprehensive approach to examine the impact of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) on the adaptivity of lung cancer cells to EGFR TKI therapies. We conducted metabolomics to trace glucose rerouting in response to PFKFB3 inhibition during TKI treatment. Live cell imaging and DCFDA oxidation were used to quantify levels of oxidation stress. Immunocytochemistry and Neutral Comet assay were employed to evaluate DNA integrity in response to therapy-driven oxidative stress.ResultsOur metabolic profiling revealed that PFKFB3 inhibition significantly alters the metabolic profile of TKI-treated cells. It limited glucose utilization in the polyol pathway, glycolysis, and TCA cycle, leading to a depletion of ATP levels. Furthermore, pharmacological inhibition of PFKFB3 overcome TKI-driven redox capacity by diminishing the expression of glutathione peroxidase 4 (GPX4), thereby exacerbating oxidative stress. Our study also unveiled a novel role of PFKFB3 in DNA oxidation and damage by controlling the expression of DNA-glycosylases involved in base excision repair. Consequently, PFKFB3 inhibition improved the cytotoxicity of EGFR-TKIs by facilitating ROS-dependent cell death.ConclusionsOur results suggest that PFKFB3 inhibition reduces glucose utilization and DNA damage repair, limiting the adaptivity of the cells to therapy-driven oxidative stress and DNA integrity insults. Inhibiting PFKFB3 can be an effective strategy to eradicate cancer cells surviving under EGFR TKI therapy before they enter the drug-resistant state. These findings may have potential implications in the development of new therapies for drug-resistant cancer treatment.

Unveiling the shared genes between systemic sclerosis and lung cancer

The risk of lung cancer is significantly increased in patients with systemic sclerosis (SSc), yet the specific genes underlying this association remain unexplored. Our study aims to identify genes shared by SSc and lung cancer. We identified differentially expressed genes (DEGs) from SSc and lung adenocarcinoma (LUAD) datasets (SSc: GSE95065, LUAD: GSE136043) in the GEO database. We found shared genes by intersecting top genes in protein–protein interaction networks by the STRING database. The area under the ROC curve (AUC) was calculated for each shared gene in validation datasets (SSc: GSE231692; LUAD: GSE43458), identifying PRKG2 as the core shared gene. We used the UALCAN platform to assess PRKG2 expression in LUAD patients at various stages and lymph node metastasis states, and compared disease-free survival (DFS) between low and high PRKG2 expression LUAD groups. PRKG2 was overexpressed in A549 cells to study its impact on lung cancer cell proliferation and invasion in vitro. We identified seven shared genes (SCN7A, AGTR1, WIF1, PRKG2, LTF, AQP4, COL10A1), with the AUC for PRKG2 exceeding 0.93 in both diseases (SSc AUC = 0.973; LUAD AUC = 0.939). The PRKG2 expression levels of LUAD patients with different clinical stages and lymph node metastasis states were consistently lower than those observed in normal individuals. The DFS of LUAD patients in the high PRKG2 expression group was higher than that in the low expression group (p = 0.028). In vitro experiments confirmed elevated PRKG2 expression inhibits the proliferation and invasion of lung cancer cells. PRKG2 is one of the genes shared by SSc and lung cancer, affecting the proliferation and invasion of lung cancer cells.

Integrative Stacking Machine Learning Model for Small Cell Lung Cancer Prediction Using Metabolomics Profiling

Background: Small cell lung cancer (SCLC) is an extremely aggressive form of lung cancer, characterized by rapid progression and poor survival rates. Despite the importance of early diagnosis, the current diagnostic techniques are invasive and restricted. Methods: This study presents a novel stacking-based ensemble machine learning approach for classifying small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) using metabolomics data. The analysis included 191 SCLC cases, 173 NSCLC cases, and 97 healthy controls. Feature selection techniques identified significant metabolites, with positive ions proving more relevant. Results: For multi-class classification (control, SCLC, NSCLC), the stacking ensemble achieved 85.03% accuracy and 92.47 AUC using Support Vector Machine (SVM). Binary classification (SCLC vs. NSCLC) further improved performance, with ExtraTreesClassifier reaching 88.19% accuracy and 92.65 AUC. SHapley Additive exPlanations (SHAP) analysis revealed key metabolites like benzoic acid, DL-lactate, and L-arginine as significant predictors. Conclusions: The stacking ensemble approach effectively leverages multiple classifiers to enhance overall predictive performance. The proposed model effectively captures the complementary strengths of different classifiers, enhancing the detection of SCLC and NSCLC. This work accentuates the potential of combining metabolomics with advanced machine learning for non-invasive early lung cancer subtype detection, offering an alternative to conventional biopsy methods.

Downregulation of tRNA methyltransferase FTSJ1 by PM2.5 promotes glycolysis and malignancy of NSCLC via facilitating PGK1 expression and translation

Fine particulate matter (PM2.5) exposure has been associated with increased incidence and mortality of lung cancer. However, the molecular mechanisms underlying PM2.5 carcinogenicity remain incompletely understood. Here, we identified that PM2.5 suppressed the expression of tRNA methyltransferase FTSJ1 and Am modification level of tRNA in vitro and in vivo. FTSJ1 downregulation enhanced glycolytic metabolism of non-small cell lung cancer (NSCLC) cells, as indicated by increased levels of lactate, pyruvate, and extracellular acidification rate (ECAR). Whereas treatment with glycolytic inhibitor 2-DG reversed this effect. In contrast, upregulation of FTSJ1 significantly suppressed glycolysis of NSCLC cells. Mechanistically, the silencing of FTSJ1 increased NSCLC cell proliferation and glycolysis through enhancing the expression and translation of PGK1. In human NSCLC tumor samples, FTSJ1 expression was negatively correlated with PGK1 expression level and the SUVmax value of PET/CT scan. In summary, our work reveals a previously unrecognized function of PM2.5-downregulated FTSJ1 on PGK1-mediated glycolysis in NSCLC, suggesting that targeted upregulation of FTSJ1 may represent a potential therapeutic strategy for NSCLC.

DNA Damage Response Network and Intracellular Redox Status in the Clinical Outcome of Patients with Lung Cancer

Background/Objectives: DNA damage response (DDR) is a network of molecular pathways associated with the pathogenesis and progression of several diseases, as well as the outcome of chemotherapy. Moreover, the intracellular redox status is essential for maintaining cell viability and controlling cellular signaling. Herein, we analyzed DDR signals and redox status in peripheral blood mononuclear cells (PBMCs) from patients with lung cancer with different response rates to platinum-based chemotherapy. Methods: Several DDR-associated signals and redox status, expressed as the GSH/GSSG ratio, were measured in two lung cancer cell lines (A549, H1299), two normal fibroblast cell lines (WS1, 1BR3hT), and PBMCs from 20 healthy controls and 32 patients with lung cancer at baseline (17 responders and 15 non-responders to subsequent platinum-based chemotherapy). Results: Higher levels of endogenous/baseline DNA damage, decreased GSH/GSSG ratios, and augmented apurinic/apyrimidinic sites, as well as lower nucleotide excision repair (NER) and increased interstrand cross-links (ICLs) repair efficiencies, were observed in lung cancer cell lines compared with normal ones (all p < 0.05). Moreover, PBMCs from patients with lung cancer showed reduced GSH/GSSG ratios, augmented apurinic/apyrimidinic sites, decreased NER and ICL repair capacities, and lower apoptosis rates, compared with healthy controls (all p < 0.001). Interestingly, PBMCs from patients who are responders are characterized by reduced GSH/GSSG ratios, augmented apurinic/apyrimidinic sites, decreased NER and ICL repair capacities, and higher apoptosis rates compared with patients who are non-responders (all p < 0.01). Conclusions: Together, DDR-associated parameters and redox status measured in PBMCs from patients with lung cancer at baseline are associated with the therapeutic benefit of platinum-based chemotherapy.

Metabolic reprogramming in lung cancer and its clinical implication

Lung cancer has posed a significant challenge to global health, and related study has been a hot topic in oncology. This article focuses on metabolic reprogramming of lung cancer cells, a process to adapt to energy demands and biosynthetic needs, supporting the proliferation and development of tumor cells. In this study, the latest studies on lung cancer tumor metabolism were reviewed, including the impact of metabolic products and metabolic enzymes on the occurrence and development of lung cancer, as well as the progress in the field of lung cancer treatment targeting relevant metabolic pathways. This provides some promising potential directions into exploring lung cancer tumor metabolism and helps researchers to better understand lung cancer.

A good response to furmonertinib fourth-line treatment of an advanced lung adenocarcinoma patient with EGFR exon20in and PIK3CA mutation: a case report and literature review

BackgroundLung cancer, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), is the most prevalent cancer globally and remains the leading cause of cancer-related mortality. Epidermal growth factor receptor (EGFR) mutations, frequently observed in female NSCLC patients, have revolutionized treatment strategies with the advent of tyrosine kinase inhibitors (TKIs). These therapies significantly improve survival and are considered the standard of care for patients harboring EGFR mutations. However, most patients eventually develop resistance to EGFR-TKIs, leading to disease progression. Resistance mechanisms are classified as either EGFR-dependent or EGFR-independent, the latter involving bypass pathway activation, including dysregulation of downstream signaling cascades. EGFR-independent resistance often renders all EGFR-TKIs ineffective, necessitating further investigation into resistance mechanisms.Case summaryWe report the case of a 63-year-old Chinese woman diagnosed with synchronous lung adenocarcinoma harboring an EGFR exon 21 far-loop insertion mutation and clear cell renal cell carcinoma (ccRCC). A multidisciplinary team recommended systemic therapy for the lung adenocarcinoma and clinical observation for ccRCC. First-line treatment with bevacizumab plus pemetrexed-carboplatin achieved a progression-free survival (PFS) of 7 months. Second-line treatment with sintilimab and nedaplatin resulted in a PFS of 4.9 months. Third-line therapy with sintilimab and anlotinib proved ineffective. In the fourth line, the patient received furmonertinib, a third-generation EGFR-TKI, based on the FAVOUR trial. This treatment achieved durable disease control with excellent tolerability, yielding a PFS of 27 months and ongoing clinical benefit.ConclusionThis case demonstrates that furmonertinib can provide significant clinical benefit to NSCLC patients with complex resistance mechanisms, including those involving the PIK3CA/mTOR pathway. These findings support its potential to overcome EGFR-TKI resistance and warrant further investigation in similar clinical contexts.

Evaluation of curcumin nanoparticles of various sizes for targeting multidrug-resistant lung cancer cells via inhalation.

Inhalation drug delivery can deliver high doses of chemotherapeutic drugs to the lung tumor. This study evaluates the efficacy and the mechanistic pathways of nebulized Cur NPs at various sizes to treat multidrug resistant lung cancer. Cur-NPs (30 nm and 200 nm) were nebulized separately onto the multidrug-resistant lung cancer cells (H69AR). Smaller NPs induced significantly higher cell death owing to a higher rate of particle internalization via dynamin-dependent clathrin-mediated endocytosis. Owing to the higher lysosome trafficking of Cur-NP30 nm compared to Cur-NP200 nm, oxidation of lysosome was higher (0.47 ± 0.08 vs 0.38 ± 0.08), contributing to significantly higher mitochondrial membrane potential loss (1.57 ± 0.17 vs 1.30 ± 0.11). MRP1 level in H69AR cells was reduced from 352 ± 12.3 ng/µg of protein (untreated cells) to 287 ± 12 ng/µg of protein (Cur-NP30 nm) and 303 ± 13.4 ng/µg of protein (Cur-NP200 nm). NF-κB, and various cytokine expressions were reduced after treatment with nebulized Cur-NPs. Nebulized Cur-NPs formulations could be internalized into the H69AR cells. The Cur-NPs toxicity toward the H69AR was size and time-dependent. Cur-NP30 nm was more effective than Cur-NP200 nm to retain within the cells to exert higher oxidative stresss-induced cell death.

OCTN1 mediates acetylcholine transport in the A549 lung cancer cells: possible pathophysiological implications

A role for acetylcholine in cell proliferation, epithelial mesenchymal transition and invasion has been well assessed and related to the presence of the non-neuronal cholinergic system in lung cancer. For the operation of this non-neuronal system, acetylcholine should be released by a transporter mediated non-quantal process. OCTN1 is one of the transporters able to catalyse acetylcholine efflux in vitro and ex vivo. Using the A549 cell line as a lung cancer model, it has been found that these cells express OCTN1 at a higher level with respect to other cancer cells. The transport capacity of OCTN1 extracted from A549 and reconstituted into proteoliposomes reflects the protein expression profile. The properties of the acetylcholine transport mediated by OCTN1 of A549 in terms of specificity to ligands and ability to catalyse efflux of acetylcholine correspond to those previously described for the same transporter in other cells or to those of the human recombinant protein. OCTN1 is the major player in acetylcholine release in A549 and, therefore, may represent a target for inhibitors able to block the acetylcholine action in this type of aggressive tumors.

Integrating necroptosis into pan-cancer immunotherapy: a new era of personalized treatment

IntroductionNecroptosis has emerged as a promising biomarker for predicting immunotherapy responses across various cancer types. Its role in modulating immune activation and therapeutic outcomes offers potential for precision oncology. MethodsA comprehensive pan-cancer analysis was performed using bulk RNA sequencing data to develop a necroptosis-related gene signature, termed Necroptosis.Sig. Multi-omics approaches were employed to identify critical pathways and key regulators of necroptosis, including HMGB1. Functional validation experiments were conducted in A549 lung cancer cells to evaluate the effects of HMGB1 knockdown on tumor proliferation and malignancy. ResultsThe Necroptosis.Sig gene signature effectively predicted responses to immune checkpoint inhibitors (ICIs). Multi-omics analyses highlighted HMGB1 as a key modulator of necroptosis, with potential to enhance immune activation and therapeutic efficacy. Functional experiments demonstrated that HMGB1 knockdown significantly suppressed tumor proliferation and malignancy, reinforcing the therapeutic potential of targeting necroptosis. DiscussionThese findings underscore the utility of necroptosis as a biomarker to guide personalized immunotherapy strategies. By advancing precision oncology, necroptosis provides a novel avenue for improving cancer treatment outcomes.

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.

The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and showed that STAG2 is uniquely tumor-suppressive among all core and auxiliary cohesin components. The heterodimeric complex components PAXIP1 and PAGR1 have highly correlated effects with STAG2 in human lung cancer cell lines, are tumor suppressors in vivo, and are epistatic to STAG2 in oncogenic KRAS-driven lung tumorigenesis in vivo. STAG2 inactivation elicits changes in gene expression, chromatin accessibility, and 3D genome conformation that impact the cancer cell state. Gene expression and chromatin accessibility similarities between STAG2- and PAXIP1-deficient neoplastic cells further relate STAG2-cohesin to PAXIP1/PAGR1. These findings reveal a STAG2-PAXIP1/PAGR1 tumor-suppressive axis and uncover novel PAXIP1-dependent and PAXIP1-independent STAG2-cohesin-mediated mechanisms of lung tumor suppression.

Red-light Emitting Orthogonally Trireactive Gold Nanoclusters for the Synthesis of Multifunctionalized Nanomaterials.

For the development of highly multifunctionalized nanomaterials, the introduction of functional molecules on gold nanoclusters containing thiols preinstalled with connecting groupsconstitutes a promising approach. However, the uniform introduction of multiple connecting groups while avoiding side reactions is a challenging task. Herein, the synthesis of gold nanoclusters (ca. 1nm) coated with thiol peptides bearing azido, amino, and aminooxy groups is reported. These nanoclusters emit red-light before and after the functionalization, enabling application to cell imaging. A detailed structure analysis using transmission electron microscope and X-ray absorption spectroscopy reveals the formation of Aun(SR)m nanoclusters as promising motifs for red-light emission. The sequential modification of the trireactive nanoclusters with RGD (Arg-Gly-Asp) peptides, metal chelators, and anticancer drugs via [3+2] cycloaddition, oximation, and amidation reactions at each functional group furnish red-light-emissive nanomaterials exhibiting remarkable toxicity against A549 human lung cancer cells. Integration of the multiligation chemistry and gold nanocluster engineering pave the way toward the development of advanced multifunctional nanomaterials for biological applications.

Exploration of Novel Metabolic Features Reflecting Statin Sensitivity in Lung Cancer Cells.

Statins are cholesterol-lowering drugs often used for the treatment of dyslipidemia. Statins also exert anti-cancer effects by inhibiting hydroxymethylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis. We previously reported that the susceptibility to statin treatment differs among cancer cells and that functional E-cadherin expression on the plasma membrane could be a biomarker of statin sensitivity in cancer cells. However, the detailed qualitative and molecular differences between statin-sensitive and statin-resistant cancer cells remain unclear. Here, we explored novel parameters related to statin sensitivity by comparing gene expression profiles and metabolite contents between statin-sensitive and statin-resistant lung cancer cell lines. We found that the expression of most cholesterol synthesis genes was lower in the statin-sensitive cancer cell line, HOP-92, than in the statin-resistant cancer cell line, NCI-H322M. Moreover, HOP-92 cells originally exhibited lower levels of CoA and HMG-CoA. Additionally, atorvastatin decreased the mRNA expression of PANK2, a rate-limiting enzyme in CoA synthesis. Atorvastatin also reduced the mRNA levels of the cholesterol esterification enzyme SOAT1, which was consistent with a decrease in the ratio of cholesterol ester to total cholesterol in HOP-92 cells. Our data suggest that the cholesterol synthetic flow and CoA content may be limited in statin-sensitive cancer cells. We also suggest that CoA synthesis and cholesterol storage may fluctuate with atorvastatin treatment in statin-sensitive cancer cells.

Synergistic inhibitory effect of atmospheric pressure plasma and berberine on non‑small cell lung cancer cells via inducing apoptosis.

Non-small cell lung cancer (NSCLC) is a type of lung cancer, the incidence and mortality rate have been high, and the use of monotherapy is easy to make patients develop tolerance. Atmospheric pressure plasma (APP) is an emerging technology for killing cancer cells in recent years, and combination of berberine (BBR) mechanism has not been fully elucidated for NSCLC. The article's primary goal is to investigate the effect of combination on NSCLC and its associated characterization. Antiproliferative effects were detected by cell viability assay and colony formation, and flow cytometry analysis of apoptosis and cycling showed that the combination synergistically induced apoptosis. Then, extracellular reactive oxygen species (ROS)levels and DCFH-DA-based kits examined intracellular ROS levels, and their effects on mitochondrial membrane potential were measured. Study reveals that co-induced apoptosis is associated with ROS accumulation. Subsequently, Western blotting (WB) detected the expression of epidermal growth factor receptor (EGFR), and the important signaling pathway proteins Ras/ERK and AKT/mTOR. Results showed that it could downregulation of EGFR protein expression and inhibit of activation of ERK/AKT signaling pathways. Simultaneous wound healing assay and epithelial-to-mesenchymal transition (EMT) marker detection were performed for the assessment of migration and EMT ability of NSCLC cells. Combination therapy inhibited migration and EMT of NSCLC cells. The results of this study show that the combination can synergistically induce apoptosis of NSCLC by regulating ROS production. EGFR downregulation and AKT/ERK signaling pathway inhibition are linked to the synergistic effect.

Chinese expert consensus on the combination of immune checkpoint inhibitors and radiotherapy for lung cancer (2025 edition)

Lung cancer has the highest incidence and mortality rates among malignant tumors in both men and women in China. According to the latest analysis of the incidence of malignant tumors released by the National Cancer Center in 2022, there were 1.0606 million new cases of lung cancer and 733 300 deaths, resulting in a significant treatment burden. In recent years, research into the mechanisms of combining immune checkpoint inhibitors with radiation therapy has deepened, and clinical evidence is rapidly accumulating, making this area a clinical focus. However, there are still many questions regarding treatment choices, highlighting the urgent need for standardized guidance. To further promote the standardization of the combined use of immunotherapy and radiation therapy in China, the National Cancer Center and the Oncology Multidisciplinary Medical Committee of Chinese Medical Doctor Association organized a group of multidisciplinary experts to conduct in-depth discussions on the synergistic mechanisms, application models, and safety of immune checkpoint inhibitors combined with radiation therapy in lung cancer (including non-small cell lung cancer and small cell lung cancer). This effort led to the formation of the "Expert consensus on immune checkpoint inhibitors combined with radiation therapy for lung cancer in China" (referred to as "the consensus"). This consensus aims to provide guidance for the combined use of immunotherapy and radiation therapy, effectively benefiting lung cancer patients.

Synthesis, Characterization, and In Vitro Analysis of a Chitosan/Gamma Alumina/Graphene Quantum Dots/Bio-Hydrogel for Quercetin Delivery to Lung Cancer Cells

Synthesis, Characterization, and In Vitro Analysis of a Chitosan/Gamma Alumina/Graphene Quantum Dots/Bio-Hydrogel for Quercetin Delivery to Lung Cancer Cells

A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD-L1 Therapy.

Combination therapy has become a promising strategy for promoting the outcomes of anti-programmed death ligand-1 (αPD-L1) therapy in lung cancer. Among all, emerging strategies targeting cancer metabolism have shown great potency in treating cancers with immunotherapy. Here, alteration in glucose and copper metabolisms is found to synergistically regulate PD-L1 expression in lung cancer cells. Thus, an intelligent biomimetic nano-delivery system is synthesized by camouflaging lung cancer cell membranes onto glucose oxidase-loaded Cu-LDHs (CMGCL) for cancer metabolism targeted interference. Such novel nanomedicine is able to induce lung cancer cell cuproptosis and PD-L1 upregulation significantly via self-amplified cascade reactions. Meanwhile, with a decent cancer cell membrane coating, CMGCL exhibited great biosafety, tumor-targeted efficiency and anti-tumor effects in LLC lung tumor-bearing mice models. Additionally, a combination of CMGCL can sensitize the therapeutic effects of αPD-L1, substantially promoting tumor inhibition in both subcutaneous and lung metastasis LLC-bearing mice models. Overall, these findings highlight the potential connections between glucose metabolism and cell cuproptosis, offering a promising approach for treating lung cancer by integrating starvation, cuproptosis, and immunotherapy.