Cisplatin-based chemotherapy remains the standard treatment for advanced non-small cell lung cancer (NSCLC); however, its efficacy is constrained by acquired drug resistance and dose-limiting toxicity. Dysregulated apoptosis is recognized as a key mechanism contributing to cisplatin resistance in NSCLC. Geniposide, an active component of traditional Chinese medicine, has demonstrated broad-spectrum antitumor activity; however, its role in cisplatin resistance remains unclear. Network pharmacology was employed to identify potential targets. The platinum-resistant A549/DDP cell line and its parental A549 line were used as in vitro models. Functional assays were performed to evaluate proliferation, apoptosis, migration, and mitochondrial membrane potential. RNA sequencing and gene knockdown/overexpression approaches were performed to investigate the underlying molecular mechanisms. An A549/DDP xenograft model was used to assess in vivo therapeutic efficacy. Network pharmacology analysis identified 125 common targets enriched in apoptosis and p53 signaling pathways. Geniposide significantly enhanced cisplatin sensitivity in A549/DDP cells by inhibiting proliferation and migration while promoting apoptosis and inducing mitochondrial membrane potential dissipation. RNA-seq identified PUMA as a key pro-apoptotic mediator. Combined treatment markedly upregulated PUMA expression, accompanied by activation of p53 signaling. Silencing of PUMA or p53 attenuated the chemosensitizing and pro-apoptotic effects, whereas PUMA overexpression independently reduced cisplatin IC₅₀ values. In vivo, geniposide combined with low-dose cisplatin achieved tumor suppression comparable to high-dose cisplatin without inducing systemic toxicity. These findings demonstrate that geniposide enhances cisplatin sensitivity in NSCLC by activating the p53-PUMA-mediated mitochondrial apoptotic pathway, thereby providing a potential strategy for overcoming chemotherapy resistance with improved safety.

The potential of Humulus scandens in delaying non-small cell lung cancer: Targeting the PI3K/Akt signaling pathway to inhibit tumor growth and metastasis.

Integrin-targeting cyclic peptides suppress TGF-β1-driven EMT and invasion in third-generation EGFR-TKI-resistant NSCLC.

Docetaxel plus ramucirumab immediately after immunotherapy in advanced NSCLC: A phase II study (DRUN).

Heterogeneous inorganic nanomedicine delivery system loaded with anlotinib for enhanced treatment of non-small cell lung cancer (NSCLC).

A resveratrol derivative RVX-208 inhibits PD-1/PD-L1 to restrain non-small cell lung cancer as an immunotherapy.

BackgroundThis study aimed to evaluate the effect of lymph node dissection technique on survival outcomes in patients who underwent surgery for clinical stage I non-small cell lung cancer.MethodsA total of 442 patients with stage I non-small cell lung cancer who underwent surgical resection at multiple centers between 2011 and 2022 were retrospectively analyzed. Patients were divided into two groups according to the lymph node dissection technique: lobe-specific lymph node dissection and systematic lymph node dissection. Survival outcomes and postoperative complications were compared between the groups. Multivariate Cox regression analysis was performed to identify prognostic factors affecting survival.ResultsPostoperative complications occurred in 86 patients (19.5%). Complications were significantly less frequent in the lobe-specific lymph node dissection group compared to the systematic lymph node dissection group (9.4% vs. 22.4%, respectively; p = 0.027). The overall annual survival rate was 68.3%. The 5-year survival rate was significantly higher in female patients than in male patients (83.6% vs. 61.7%, p < 0.001). The 5-year survival rate was 69.3% in patients who underwent systematic lymph node dissection and 64.8% in those who underwent lobe-specific lymph node dissection, with no statistically significant difference between the two techniques (p = 0.332). In multivariate Cox regression analysis, advanced age was not a significant predictor of survival (p = 0.119, HR = 0.714, 95% CI: 0.467-1.090), whereas male gender was identified as an independent poor prognostic factor (p = 0.01, HR = 2.781, 95% CI: 1.506-5.138).ConclusionsLymph node dissection remains a critical component of surgical treatment in early-stage lung cancer. The comparable survival outcomes and lower complication rates observed with lobe-specific lymph node dissection suggest that it may be a preferable option in selected patients with stage I non-small cell lung cancer. Nevertheless, prospective multicenter studies are required to confirm these findings.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality in California, with Non-Hispanic Black (NHB) patients experiencing the highest mortality rates. Disparities in receipt of guideline-concordant treatment (GCT) contribute to these outcomes. This population-based study analyzed racial and ethnic differences in GCT receipt among early-stage NSCLC patients. Patients diagnosed with early-stage NSCLC (tumors ≤ 4cm, no lymph node involvement, and no distant metastases) between 2012 and 2022 were identified from the Los Angeles County Cancer Surveillance Program. Logistic regression evaluated associations between race/ethnicity and receipt of GCT (surgery or radiation only vs. no treatment or multiple treatments), adjusting for potential confounders. In our sample (n = 2,857), the average age was 69.6years, 63.2% were female, mean tumor size was 1.9cm, and the cohort was 57.3% Non-Hispanic White (NHW), 8.9% NHB, 14.2% Hispanic, and 18.8% Asian/Pacific Islander (API). While most patients (87.4%) received GCT, NHB and Hispanic patients had higher rates of non-GCT treatment (18.0% and 15.8%, respectively; p <0.001). NHB patients had significantly higher odds of not receiving GCT compared with NHW patients (OR: 1.55, 95% CI: 1.07-2.26; p < 0.05). No significant differences were observed for API or Hispanic patients. Addressing disparities in GCT for patients diagnosed with early-stage NSCLC is critical to improving survival outcomes. Future studies identifying factors influencing a patient's and physician's decision to receive, recommend, and adhere to GCT guidelines are needed to understand the complexity of treatment decision-making.

Relapsed small cell lung cancer (SCLC) treatment has limited evidence-based options. Solvent-based paclitaxel (PTX) and albumin-bound nanoparticle paclitaxel (nab-PTX) are commonly prescribed though never comprehensively quantified. A systematic review and single-arm meta-analysis was conducted (PROSPERO Registration: CRD42024592475). PubMed, Web of Science, Cochrane Library, and EMBASE were searched for interventional or observational studies reporting PTX or nab-PTX monotherapy in relapsed SCLC. Primary outcomes were the pooled 3-month progression-free survival rate (PFS), 6-month overall survival rate (OS), objective response rate (ORR), and disease-control rate (DCR). Random-effects models generated pooled estimates; prespecified subgroup analyses compared Asian versus Euro-American cohorts, and PTX versus nab-PTX treatment. Fifteen studies (11 retrospective and 4 prospective) comprising 631 patients met the eligibility criteria of the study. Pooled efficacy estimates were: 3-month PFS 39% [95% confidence interval (CI)=28-50%, I2=84%], 6-month OS 46% (95%CI=32-61%, I2=91%), ORR 16% (95%CI=12-21%, I2=51%) and DCR 51% (95%CI=41-61%, I2=83%). Grade 3 or higher toxicities were infrequent - neutropenia 18% (95%CI=11-25%, I2=89%) and peripheral neuropathy 2% (95%CI=0-3%, I2=0%). Among 45 patients with pre-existing interstitial lung disease (ILD), treatment-related ILD exacerbations were 17% (95%CI=6-28%, I2=0%). Asian cohorts demonstrated greater neutropenia (26% vs. 5%) than Euro-American cohorts. Efficacy and safety were similar between PTX and nab-PTX monotherapy. Despite substantial heterogeneity, paclitaxel-based regimens demonstrated modest but clinically meaningful activity with generally favorable safety profile in relapsed SCLC, highlighting them as a pragmatic salvage option. In patients with ILD, their use warrants caution due to the risk of ILD exacerbation.

Minimally Invasive/Robotic Surgery for Lung Cancer.

Mapping the immune microenvironment of non-small cell lung cancer.

Minimally invasive surgery is the gold standard to perform pulmonary lobectomy for early-stage non-small cell lung cancer. Recently, non-intubated video-assisted thoracoscopic surgery (NI-VATS), based on spontaneous ventilation under sedation and regional anaesthesia, has emerged as less invasive alternative to conventional anaesthesia, reporting several benefits but its application in major pulmonary resection remains controversial. We present the first report of robotic-assisted surgery (RATS) to perform a right lower lobectomy with radical lymph-node dissection in a non-intubated patient presenting a pulmonary adenocarcinoma. In our experience, this approach is feasible, combining the ergonomic and precision advantages of robotic technology with the potential physiological benefits of spontaneous ventilation further reducing the invasiveness of both surgery and anaesthesia This innovative combination may be defined as non-intubated robotic-assisted thoracic surgery: NI-RATS.

Prospective clinical implementation of the robust optimization planning technique in long-course photon radiotherapy treatment for lung cancer.

Immunotherapy has become a primary treatment for advanced non-small cell lung cancer (NSCLC), although drug resistance is inevitable. Radiotherapy enhances immunotherapy efficacy, particularly in early to mid-stage NSCLC. However, the synergistic effects of radiotherapy and immunotherapy in advanced NSCLC remain controversial. We retrospectively analyzed data from 141 stage IV NSCLC patients treated with first-line immunotherapy or chemoimmunotherapy at Hangzhou Cancer Hospital. Patients were divided into groups receiving radiotherapy combined with immunotherapy versus immunotherapy alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Cox regression method. Subgroup Cox regression analyses were performed to optimize the combination regimens. The combined therapy group showed longer PFS (16.9 vs. 8.49 months, HR 0.57, p = 0.006) and OS (69.93 vs. 24.62 months, HR 0.60, p = 0.04). Subgroup analysis indicated that non-squamous NSCLC patients without immunotherapy rechallenge benefited most. Radiotherapy added to immunotherapy in lung or brain metastases showed a trend toward improved PFS (lung: 19.34 vs. 6.03 months, HR 0.62, p = 0.30; brain: 22.72 vs. 7.80 months, HR 0.59, p = 0.29). Concurrent (HR 0.41, p = 0.02) or consolidation radiotherapy (HR 0.32, p = 0.003) during immunotherapy offered greater PFS benefits than symptom-relief radiotherapy. Both stereotactic body radiotherapy and conventional radiotherapy yielded similar survival outcomes. Incidence of grade 3 or higher pneumonia post-lung-radiotherapy was 3.45%. Our study highlights the synergistic efficacy of combining radiotherapy with immunotherapy in advanced NSCLC. Optimizing patient selection, targeting specific sites, effective timing, and tailored radiotherapy regimens significantly improved PFS and OS, providing crucial insights for enhancing clinical outcomes in advanced NSCLC.

Antibody-drug conjugates (ADCs) are covalently conjugated molecules composed of a monoclonal antibody, a payload, and a linker. They represent an innovative therapeutic approach that combines the precise targeting capability of target therapies with the cytotoxic effects of chemotherapeutic agents. Given the unique molecular structure of ADCs, drug-related adverse reactions have drawn a considerable attention. Based on the safety data of ADCs currently available in the field of lung cancer, the common adverse drug reactions primarily involve the digestive system, hematologic system, hepatobiliary system, pulmonary system, skin, eyes, sensory nervous system, and musculoskeletal system. Unlike other cancer types, lung cancer is characterized by complex disease subtypes and molecular pathological mechanisms, as well as diverse treatment modalities. Moreover, patients with advanced lung cancer often have comorbidities such as chronic obstructive pulmonary disease and pulmonary inflammation, making the comprehensive management of ADC-related adverse reactions even more challenging. To address this, the Precision Treatment Branch of Thoracic Oncology, Chinese Geriatric Health Association, has taken the lead in organizing a multidisciplinary panel of domestic experts in gastroenterology, dermatology, respiratory medicine, ophthalmology and oncology, to discuss and jointly formulate the "Consensus of Chinese experts on the multidisciplinary management of adverse reactions to antibody-drug conjugates in the treatment of Lung Cancer (2025 edition)". A total of 21 recommendations are proposed in this consensus, covering pre-ADC safety assessments, comprehensive monitoring and management of relevant adverse reactions during ADC treatment, patient education, and medication guidance for special populations. The consensus aims is to provide clinicians with practical guidelines for the application of ADC, thereby maximizing therapeutic benefits for patients with lung cancer.

The rearranged during transfection (RET) gene is a proto-oncogene encoding a receptor tyrosine kinase. RET gene alterations are driver events in various tumors. Pralsetinib and selpercatinib are novel, highly selective RET tyrosine kinase inhibitors (RET-TKIs). They are recommended as priority therapeutic options for RET fusion-positive non-small cell lung cancer (NSCLC) in the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer and Thyroid Carcinoma and the Chinese Medical Association (CMA) Clinical Guidelines for Lung Cancer, as well as for radioiodine-refractory differentiated thyroid cancer with RET fusion and RET-mutant medullary thyroid carcinoma. Common adverse events asosociated with pralsetinib and selpercatinib include hypertension, liver enzyme abnormalities, neutropenia and fatigue. Studies have demonstrated that the incidence of adverse events is not associated with disease type. Given the low prevalence of RET gene alterations (＜5%), which are regarded as rare genetic mutations, clinical experience in the use pf RET-TKIs and and patient management remains limited. Base on the current status of adverse event management of RET-TKIs in China, and integrating the latest international evidence and clinical experience, the Chinese Medical Doctor Association Tumor Multidisciplinary Diagnosis and Treatment Professional Committee and the Shenzhen Medical Doctor Association Tumor Multidisciplinary Diagnosis and Treatment Professional Committee organized discussion among experts from medical oncology, respiratory medicine, radiation oncology, thoracic surgery, and other related disciplines to formulate this expert consensus on the management of adverse events of RET-TKIs.

Chemoimmunotherapy has become the standard first-line treatment for advanced non-small cell lung cancer (NSCLC). Deciphering the T-cell subset responsible for chemoimmunotherapy and easily tested conveniently is critical in predicting the treatment outcomes. Based on peripheral blood collected from patients enrolled from a phase 2 clinical study (ClinicalTrials.gov NCT04836728), we performed multi-color flow cytometry and unsupervised analysis to explore correlations with therapeutic outcomes. We integrated single-cell RNA and T-cell receptor (TCR) sequencing in 36 samples, including peripheral blood, tumors and non-tumor tissues, from 8 NSCLC patients to interpret the correlation, which was further verified using blood samples, orthotopic and subcutaneous lung cancer mouse model. The baseline CD28-KLRG1+CD57+ and on-treatment CD28-KLRG1+ CD8+ T cells in peripheral blood were independent factors which indicated improved treatment outcomes in advanced NSCLC patients receiving first-line chemoimmunotherapy. While being in a late-differentiated T-cell status, these cells were clonally expanded and reinvigorated during chemoimmunotherapy, serving as a peripheral T-cell pool for supplying potential tumor-reactive T cells in tumors, and reversely differentiating into less-differentiated subsets. The zinc-metallothionein pathway regulated the CD28-KLRG1+ CD8+ T-cell subset. Zinc supplementation combined with chemoimmunotherapy improved both local and systemic antitumor immune responses in mouse model. Circulating CD28-KLRG1+ CD8+ T cells are valuable and convenient biomarkers for first-line chemoimmunotherapy in advanced NSCLC and provide insight into how late-differentiated or senescent T cells engage in the antitumor immunity when immunotherapy is added to conventional therapies.

Timely and accurate Computed Tomography (CT) screening is crucial for the early clinical treatment of lung cancer and preventing the progression of malignant pulmonary nodules. However, owing to the large scale variations and blurred boundaries of lesions, existing deep learning models struggle to strike an optimal balance between computational costs, receptive field size, and the precise reconstruction of fine details. To address these challenges, this paper integrates three complementary components-A2C2f_DFFN, SPPF_LSKA, and DySample-into the YOLOv12n framework to construct PD-YOLO, a high-precision fine-grained lung cancer detection model. The main contribution lies in the synergistic optimization of these modules for CT‑based pulmonary lesion detection, rather than the theoretical novelty of any single component. Specifically, we introduce the A2C2f_DFFN module, which utilizes a Dynamic Feed-Forward Network to significantly enhance the non-linear feature representation of low-contrast early lesions. Furthermore, the SPPF_LSKA module is designed by combining Spatial Pyramid Pooling with Large Separable Kernel Attention, which expands the effective receptive field with extremely low computational overhead to handle large-scale massive tumor consolidations typical of advanced lung cancer. Additionally, an ultra-lightweight dynamic upsampling module (DySample) is employed to adaptively reconstruct high-resolution features, effectively mitigating the loss of edge textures and minor infiltrates during feature propagation. Extensive experiments on a chest CT dataset containing 4200 images demonstrate that PD-YOLO achieves a mean Average Precision (mAP @0.5) of 97.3%, outperforming state-of-the-art detectors including YOLOv12s and YOLOv12n. The proposed model successfully optimizes the trade-off between missed detections and false alarms, exhibiting highly robust overall object detection capabilities for complex clinical applications, particularly in the automated screening and localization of malignant pulmonary lesions.

Prophylactic cranial irradiation (PCI) has traditionally been a cornerstone of treatment in limited-stage and extensive-stage small cell lung cancer (SCLC). Recent evidence suggests that active MRI brain surveillance may result in comparable overall survival (OS) and progression-free survival (PFS). This systematic review and meta-analysis aims to compare patient outcomes between PCI and active MRI brain surveillance. Medline, Embase, Cochrane Library, Scopus and Web of Science databases were searched from inception until 30th April 2025 to identify all studies comparing PCI against active MRI brain surveillance in adult SCLC patients. Risk ratios (RR) and hazard ratios (HR) were pooled and analysed using a random-effects model. Fourteen studies comprising 2881 patients were included. In patients with limited-stage SCLC, PCI significantly improved OS (HR 0.67, 95% CI 0.53-0.84, p < 0.01), PFS (HR 0.77, 95% CI 0.65-0.91, p < 0.01), and brain metastasis (BM) incidence (RR 0.58, 95% CI 0.45-0.76, p < 0.01). In patients with extensive-stage SCLC, PCI only significantly reduced BM risk (RR 0.49, 95% CI 0.29-0.81, p < 0.05), but was not associated with significant improvement in OS (HR 0.89, 95% CI 0.61-1.28, p = 0.52) or PFS (HR 0.90, 95% CI 0.60-1.36, p = 0.62). While PCI reduces BM incidence in both limited-stage and extensive-stage SCLC, its survival benefits are confined to limited-stage SCLC. Active MRI brain surveillance may be preferred in extensive-stage disease due to comparable survival outcomes and reduced toxicity. CRD42024529707 [PROSPERO].

To construct AS1411 aptamer-modified mesoporous polydopamine (MPDA) nanoparticles co-loaded with doxorubicin (DOX) and catalase (AS1411-D/C-MPDA nanoparticles) targeting the tumor microenvironment and evaluate their efficacy in synergy with ultrasound for inhibiting Lewis lung carcinoma (LLC) cells. AS1411-D/C-MPDA nanoparticles were synthesized using a one-step assembly method, and their physicochemical properties were characterized. Cultured LLC cells were treated with free DOX, DOX-loaded MPDA nanoparticles or AS1411-D/C-MPDA nanoparticles with or without ultrasound exposures (frequency 1.0 MHz and intensity 1.0 W/cm²) for 3 min. The changes in viability, apoptosis, and migration and invasion abilities of the cells were assessed using CCK-8 assay, flow cytometry (Annexin V-FITC/PI staining), wound healing assay, and Transwell assay, respectively. The prepared AS1411-D/C-MPDA nanomaterials showed a uniform spherical morphology, a mean particle size of 183.36±15.99 nm, and DOX and catalase encapsulation efficiencies of (91.17±0.08)% and (29.59±0.2)%, respectively. The nanoparticles demonstrated good pH responsiveness to enable disintegration for promoting drug release, with a cumulative DOX release rate of (81.25±1.61)%. The nanoparticles possessed strong oxygen-generating capacity to alleviate cell hypoxia. AS1411-modified nanoparticles showed significantly enhanced cellular uptake by LLC cells. Compared with free DOX and DOX-MPDA nanoparticles combined with ultrasound, AS1411-D/C-MPDA in synergy with ultrasound induced higher levels of ROS in LLC cells, resulted in a higher cell apoptosis rate, and more efficiently reduced cell viability and suppressed cell migration and invasion. AS1411-D/C-MPDA nanoparticles combined with ultrasound allow targeted delivery of anticancer drugs and represent a promising strategy for synergistic treatment of lung cancer by integrating physical acoustics, pharmaceutical chemistry, and tumor microenvironment regulation.