Search Results (6,117)

This systematic review examines the emerging interplay between ferroptosis and disulfidptosis, two distinct forms of regulated cell death (RCD) centered on the SLC7A11 (also known as xCT)-mediated metabolic paradox. Traditionally recognized as a potent anti-ferroptotic factor, SLC7A11 imports cystine for glutathione synthesis to neutralize iron-dependent lipid peroxidation. However, the discovery of disulfidptosis identifies SLC7A11 as a metabolic liability, representing a paradigm shift in our understanding of cellular antioxidant defense. This discovery reveals a transformative vulnerability in SLC7A11-overexpressing cells, shifting the focus from conventional survival mechanisms to the consequences of catastrophic structural collapse. Beyond metabolic exhaustion, this review highlights the role of metal dyshomeostasis as a primary driver, spanning from iron-catalyzed ferroptosis to copper-mediated metabolic interference. This conceptual framework redefines the SLC7A11 axis as a targetable “double-edged sword” in therapy-resistant malignancies. Clinical synthesis of multi-omic gene signatures, such as the disulfidptosis- and ferroptosis-related gene prognostic score (DRGPS) and the ferroptosis- and disulfidptosis-related gene (FDRG) scores, demonstrates their robust value in prognostic stratification and in predicting immunotherapy response across malignancies, including lung adenocarcinoma and hepatocellular carcinoma. Furthermore, we evaluate the capacity of disulfidptosis to prime immunogenic cell death (ICD) and remodel the immunosuppressive tumor microenvironment to bypass chemoresistance. By integrating mechanistic insights with clinical data, this review provides a comprehensive framework for targeting the SLC7A11 axis as a transformative therapeutic vulnerability in precision oncology. Full article

Background/Objectives: Pulsed Electric Field (PEF) therapy is a non-thermal ablation technique that induces immunogenic cell death through high-voltage, short-duration electrical pulses. This may enhance antitumor immunity by releasing intact tumor antigens and potentially generating abscopal effects. We report early outcomes in 32 patients with primary lung cancer or lung oligometastases treated with PEF at a community hospital, with a median (IQR) follow-up of 180.5 (158–207) days. Methods: This retrospective study collected demographics, cancer type, treatment response, and outcomes for patients undergoing PEF ablation. Tumor response was assessed using Sum of Longest Dimensions per RECIST 1.1 to classify progressive disease, stable disease, partial response, or complete response. Volumetric changes were additionally analyzed using RECIST 1.1 percentage thresholds applied to change in volume. Results: At initial 3-month follow-up, 26 of 32 patients demonstrated stable disease, partial response, or complete response, suggesting an 81.25% disease control rate/clinical benefit rate among this cohort. Among patients with Stage III–IV disease, 27.6% (8/29) showed radiographic evidence of a possible abscopal response. At 6 months, 24 of 32 patients remained alive and evaluable, with 62.5% (20/32) maintaining stable disease, partial response, or complete response. Conclusions: Despite patients having progressive disease on systemic therapy before PEF, early outcomes post-ablation suggest favorable local control and potential immunologic benefit. Patients with early-stage disease not receiving systemic therapy also showed excellent local response. Patients tolerated therapy very well. Clinical benefit was observed in 81.25% of patients at 3 months and 62.5% at 6 months, with radiographic evidence of possible abscopal responses in 27.6% of advanced-stage patients, supporting further exploration of the immunogenic potential of PEF demonstrated in preclinical and emerging clinical studies. Full article

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality despite major advances in diagnostics and therapies. The prognosis remains poor, mostly due to late-stage presentation and molecular heterogeneity. Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. The development of EGFR tyrosine kinase inhibitors (TKIs) has significantly improved outcomes in patients with EGFR mutations. Variant allele frequency (VAF) is a quantitative genomic measure representing the proportion of sequencing reads harboring a given mutation. In NSCLC tissue, the EGFR mutation VAF reflects tumor clonality and intratumoral heterogeneity, and accumulating evidence suggests an association between EGFR VAF and response to EGFR-targeted TKIs. Methods: To address the limited synthesis of data on the relevance of EGFR mutation VAF in NSCLC, we conducted a narrative review of the literature using PubMed/MEDLINE and Embase databases and current clinical guidelines, synthesizing available evidence on EGFR VAF, including its biological, molecular, and therapeutic implications in EGFR-mutated disease. The review was structured in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) checklist. Results: EGFR VAF and on-treatment VAF dynamics are consistently associated with treatment response, progression-free survival, and overall survival in osimertinib-treated NSCLC. Baseline VAF enables risk stratification, early clearance kinetics predict durable benefit, and longitudinal VAF monitoring facilitates early detection of resistance. Importantly, the prognostic implications of VAF differ fundamentally between tissue-based and plasma-based measurements: high tissue VAF reflects clonal homogeneity and predicts favorable TKI response, whereas high plasma VAF indicates elevated tumor burden and is associated with inferior outcomes. In the second-line setting, the T790M/activating mutation ratio serves as a surrogate for resistance clonality and independently predicts osimertinib efficacy. Conclusions: EGFR VAF represents a promising dynamic molecular biomarker for treatment monitoring and precision decision-making in EGFR-mutated NSCLC. Full article

Background/Objectives: Liquid biopsy (LB) is transforming cancer care by enabling minimally invasive tumor profiling. While current research and clinical pathways mostly focus on blood LB, sputum represents a non-invasive, readily available respiratory specimen that may offer unique advantages for lung cancer (LC) care. Despite its potential, the maturity, breadth, and clinical applicability of sputum-based LB remain elusive. Methods: We conducted a scoping review to systematically map the existing literature on sputum LB in LC. Electronic databases were searched for studies evaluating sputum-derived biomarkers—cytologic, genomic, epigenetic, transcriptomic, proteomic, metabolomic, metagenomic, and extracellular vesicle–derived products—across the LC care continuum. Study designs, technologies, clinical contexts, and reported outcomes were extracted and synthesized qualitatively. Results: The literature demonstrated substantial heterogeneity in sputum collection, processing, and analytical platforms. Early work focused on cytometry and genetic alterations, while recent studies increasingly explore DNA methylomics, microRNAs, extracellular vesicle-derived products, and multi-omics approaches. The evidence suggests potential utility of sputum biomarkers for early detection and risk stratification, particularly in high-risk populations, with emerging data supporting roles in molecular subtyping, response monitoring, prognostication, and surveillance. However, few studies report prospective validation, direct comparison with blood-based LB, or impact on actual patient outcomes. Conclusions: Sputum LB is a promising yet underdeveloped modality in LC care. This scoping review highlights technological innovations alongside significant methodological heterogeneity and translational gaps. Future research should focus on standardization, prospective validation, impact on patient outcomes, and integration with blood- and other body fluid–based LB, as well as imaging biomarkers. This will enable incorporation of sputum-based LB into actual clinical pathways of LC care. Full article

Oncogenic driver mutations in non-small cell lung cancer (NSCLC) activate defined signaling pathways that sustain tumor growth and influence the immune landscape. Yet, how coordinated interactions among diverse cell populations within the tumor immune microenvironment (TIME) contribute to this process remains largely unresolved. To address this, we profiled approximately 200,000 single cells from 45 treatment-naïve NSCLC patients representing seven major driver mutations. This analysis uncovered five multicellular modules (CM1–5) with distinct functional properties, each linked to specific malignant regulatory programs. Among them, CM2 and CM5 exhibited pronounced invasive features and were associated with unfavorable clinical outcomes. CM2 was predominantly observed in EGFR- and MET-driven brain metastases and was defined by strong crosstalk between astrocytes and myofibroblasts. Factors such as SPP1, PTN, and PSAP, together with metabolic alterations, contributed to a microenvironment supportive of metastatic colonization in the brain. By contrast, CM5 was enriched in ROS1-, KRAS-, and EGFR-mutant tumors and consisted of diverse myeloid and endothelial subsets characterized by immunosuppressive and pro-angiogenic signaling, including MIF, GALECTIN, and RETN, collectively facilitating immune escape and vascular remodeling. We further constructed and validated a driver mutation-specific prognostic signature (DMSP.sig) model integrating receptor–ligand interactions and core transcription factors, which effectively stratified patient survival. Leveraging this model, we also identified potential therapeutic candidates linked to these prognostic features, highlighting opportunities for clinical intervention. In summary, our study delineates how oncogenic drivers give rise to distinct TIME architectures, providing a framework for prognostic assessment and precision immunotherapy in high-risk NSCLC. Full article

Preoperative sarcopenia has emerged as an important determinant of adverse postoperative and long-term outcomes in patients with resectable non-small cell lung cancer (NSCLC). Its frequent coexistence with systemic inflammation may further worsen survival outcomes. At the same time, neoadjuvant chemotherapy and chemoimmunotherapy have substantially improved pathological response and survival in resectable NSCLC. However, their interaction with host-related factors such as sarcopenia and systemic inflammatory status remains insufficiently characterized. This narrative review aims to synthesize current evidence regarding the interplay between preoperative sarcopenia, systemic inflammation, and neoadjuvant therapy in resectable NSCLC and evaluates their potential combined impact on surgical and oncological outcomes. A narrative synthesis of 20 studies involving patients undergoing lung cancer resection was performed. Sarcopenia was primarily assessed using computed tomography or PET-CT-derived skeletal muscle indices, most commonly the skeletal muscle index, whereas systemic inflammation was evaluated using biochemical inflammatory markers. The available evidence consistently indicates that preoperative sarcopenia is associated with poorer long-term survival, and this adverse effect appears to be amplified in the presence of systemic inflammation. Although neoadjuvant chemoimmunotherapy has improved tumor response and survival outcomes, it may also act as a systemic stressor capable of aggravating muscle loss. Importantly, no study to date has simultaneously evaluated sarcopenia, systemic inflammation, and neoadjuvant therapy within a unified analytical framework. Most available studies focus primarily on sarcopenia, while inflammatory or treatment-related parameters are typically analyzed separately. Overall, while sarcopenia and systemic inflammation are recognized predictors of adverse outcomes in resectable NSCLC, robust evidence integrating them with neoadjuvant therapy is lacking. Clarifying their potential interaction may improve risk stratification and help to optimize perioperative management strategies in the era of neoadjuvant therapy. Full article

Since tumor spread through air spaces (STAS) was first described over a decade ago, numerous studies have demonstrated that it is a high-risk prognostic feature in non-small cell lung cancer (NSCLC). However, due to preoperative and intraoperative limitations in pathologic diagnosis, STAS is generally diagnosed following curative intent resection. While STAS should influence NSCLC treatment strategy—particularly upfront surgical decision-making—postoperative diagnosis of STAS has heretofore limited this possibility. While limited to retrospective studies, the current evidence suggests that patients with tumor STAS should undergo a more extensive anatomical resection—preferably a lobectomy, if they are candidates. These results are particularly important in the setting of the results of the JCOG0802 and CALGB 140503 randomized controlled trials which have begun a paradigm-shift toward sublobar resections for early-stage NSCLC, which may not hold similar benefit for early-stage STAS+ disease. The aims of this review are to: (1) detail the current evidence concerning choice of resection extent for STAS+ disease, (2) summarize the current evidence about optimum surgical margins for STAS+ disease, (3) detail the potential role for adjuvant chemotherapy in early-stage STAS+ disease, (4) assess the current limitations in preoperative STAS risk prediction and intraoperative STAS detection, and (5) highlight promising AI-based advancements which will allow surgeons to risk-stratify STAS probability or confirm STAS status intraoperatively. The main limitation of this review is the reliance on retrospective studies as there is a current lack of prospective or randomized data within STAS+ NSCLC, particularly regarding optimal resection strategy for STAS+ disease. Full article

Emphysema is a well-recognized risk factor for lung cancer; however, its influence on the immunologic tumor microenvironment in lung adenocarcinoma remains poorly defined. In this pilot, hypothesis-generating study, immune-related gene expression profiling was performed using archival formalin-fixed paraffin-embedded tumor specimens from 12 patients with lung adenocarcinoma, including the Never-smoker group (never-smokers without emphysema; n = 4), the Smoker 1 group (smokers without emphysema; n = 3), and the Smoker 2 group (smokers with CT-defined emphysema; n = 5). Expression of 770 immune-related genes was analyzed using the nCounter PanCancer IO 360 Panel (NanoString Technologies, Seattle, WA, USA). Compared with the Never-smoker group, tumors from the Smoker 1 group showed marked upregulation of SFRP1, SERPINB5, and IL6, whereas tumors from the Smoker 2 group exhibited increased expression of KIR2DL3, BLK, and WNT2B. Relative to the Smoker 1 group, the Smoker 2 group demonstrated significant upregulation of MMP7, TDO2, and CCL18. Pathway enrichment analysis revealed cytokine–cytokine receptor interaction as the most prominently enriched pathway in both smoker groups, while the IL-17 signaling pathway was preferentially enriched in the Smoker 2 group. In addition, diffusing capacity for carbon monoxide showed significant correlations with immune-related genes including IL-6 and IL-6R. Collectively, these preliminary findings suggest that lung adenocarcinoma arising in emphysematous lungs may be characterized by a distinct pro-inflammatory immune microenvironment. Given the small sample size and potential confounders, these results should be regarded as hypothesis-generating. Emphysema-associated immune remodeling may nevertheless represent an important biological factor worthy of validation in larger, independent cohorts. Full article

Objective: To characterize the frequency, timing, patterns of first distant metastasis, and post-metastatic survival in uterine sarcoma using population-based registry data. Methods: This study included all patients diagnosed with uterine sarcoma between 2000 and October 2025 in the regional cancer registry of Saxony-Anhalt, Germany. Patients with carcinosarcoma were excluded. Metastatic disease was classified as primary (present at diagnosis or ≤3 months) or metachronous (>3 months). Metastatic patterns were analyzed based on the first metastatic presentation only. Overall survival (OS), recurrence-free survival (RFS), and post-metastatic OS were estimated using Kaplan–Meier methods. RFS was defined as the interval from confirmed tumor-free status after primary therapy to first recurrence or death, and was restricted to patients who achieved tumor-free status (n = 114). Multivariable Cox regression analyses for OS and RFS were performed with administrative censoring at 5 years. Results: A total of 155 patients with uterine sarcoma were included. During follow-up, 54 patients (34.8%) were diagnosed with metastatic disease, of whom 30 (55.6%) presented with primary metastatic disease. Lung was the most frequent site of first metastasis, followed by bone, peritoneum, and liver; 43.4% of metastatic patients had multiple synchronous metastatic sites at first presentation. Median time to first metastasis was short, with several metastatic sites showing median values of zero months, reflecting the high proportion of primary metastatic disease. Median post-metastatic OS was 12 months. Advanced FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage and failure to achieve tumor-free status after primary therapy were independently associated with worse OS, whereas histologic subtype was not. Conclusions: In this population-based cohort, metastatic disease occurred in more than one-third of patients with uterine sarcoma and was frequently present at diagnosis. Lung metastases predominated as the first site of distant spread, and post-metastatic survival was poor. These findings underscore the importance of comprehensive staging at diagnosis and highlight the aggressive metastatic behavior of uterine sarcoma in real-world practice. Full article

Backgrounds/Objectives: Non-small cell lung cancer (NSCLC) exhibits substantial prognostic heterogeneity that is not fully captured by conventional anatomical staging, highlighting the need for individualized risk assessment. Radiomics enables non-invasive characterization of tumor phenotype, yet high dimensionality and inter-feature correlations often limit model stability and interpretability. Methods: To address these challenges, we developed a multimodal late-fusion framework integrating radiomic, clinical, and demographic information to predict patient-specific absolute risk in the Lung1 cohort (N = 398). Radomic features (N = 107) were extracted from primary tumor volumes and refined using a Group Lasso–penalized Cox model, preserving biological coherence and producing a parsimonious imaging signature. This signature was combined with clinical and demographic variables using five different late-fusion strategies: weighted averaging, Cox regression, logistic stacking, Random Survival Forests (RSF), and XGBoost. Model performance was evaluated using 5-fold cross-validation based on discrimination, calibration, and risk stratification metrics. Results: Using 5-fold cross validation, the radiomics-only model outperformed conventional clinical staging in patients’ risk prediction (C-index 0.5717 vs. 0.5350) and accuracy, demonstrating the prognostic value of imaging biomarkers. All fusion strategies improved risk prediction performance, with the Cox fusion model slightly better than other fusion methods with C-index of 0.58, time-dependent AUC of 0.60, and the distinct risk stratification with log-rank χ² of 22.85. Conclusions: These findings suggest that multimodal late fusion may provide robust and interpretable risk estimates with potential clinical relevance, supporting personalized risk prediction for informed decision-making in NSCLC. Full article

Background: Liquid biopsy-based biomarkers provide valuable insights into tumor biology, dynamics, burden, relapse prediction and therapeutic responsiveness. The stress-inducible heat shock protein 70 (Hsp70), which is frequently overexpressed in highly aggressive solid tumors and is presented on the cell membrane of tumors but not normal cells, is found in the circulation either as a free protein originating from dying cells or in the context of extracellular vesicles (EVs) that are actively released by viable tumor cells. This study demonstrates the potential value of circulating Hsp70 (eHsp70) levels across multiple solid tumor entities as an entity- and stage-dependent diagnostic biomarker reflecting tumor burden and disease stage. Methods: Circulating eHsp70 levels, as determined using the Hsp70-exo ELISA which detects free and EV-associated Hsp70, in plasma samples collected from patients with different tumor entities (n = 389) prior to the initiation of any oncological therapy and healthy controls (n = 108) between 2021 and 2025, were analyzed retrospectively. Tumor stages were categorized as early, locally advanced, or metastatic. The Kruskal–Wallis test was used for group comparisons and the Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic performance of eHsp70 levels. DeLong’s test was used to calculate differences between AUC values. Results: In tumor patients (n = 389), circulating eHsp70 levels were significantly higher than those in healthy controls (n = 108) (Kruskal–Wallis, p < 0.001). eHsp70 levels progressively increased from early-stage to locally advanced and metastatic disease in a stage-dependent manner. Although ROC analysis demonstrated the limited discriminatory performance of eHsp70 levels in early-stage disease (AUC 0.569), increased discrimination was apparent in locally advanced disease (AUC 0.751), metastatic tumors (AUC 0.784) and combined advanced tumor diseases (AUC 0.765; significant by DeLong’s Test comparing early-stage to locally advanced and metastatic tumors), irrespective of the tumor entity with the highest AUC values in metastatic breast cancer (AUC 0.872), sarcoma (AUC 0.861) and non-small cell lung cancer (NSCLC) (AUC 0.835). Apart from minor entity-specific differences, the correlation of eHsp70 levels with the tumor stage remained consistent across all measured tumor entities. Conclusions: Circulating eHsp70 levels are markedly elevated in patients with highly malignant solid tumors and show a consistent, stage-dependent increase across multiple tumor types. These findings suggest that circulating eHsp70, as an indicator of tumor-associated cellular stress and overall tumor burden, represents a valuable biomarker for assessing disease stage, monitoring disease progression, and evaluating therapeutic responses. Full article

Background/Objectives: Cancer cachexia (CC) is a metabolic syndrome characterized by the progressive loss of skeletal muscle and adipose tissue during tumor progression. Despite its clinical prevalence, effective therapeutic options are currently lacking. Phloretin, a natural flavonoid with potent anti-inflammatory and antioxidant properties, has unclear efficacy against CC. This study investigates the therapeutic potential of phloretin in ameliorating cancer cachexia. Methods: Mouse models of CC were established using BALB/c mice implanted with C26 colon carcinoma cells and C57BL/6 mice implanted with Lewis lung carcinoma (LLC) cells. Upon the detection of palpable tumors, phloretin (10 mg/kg) was administered daily via intraperitoneal injection. At the endpoint, hind limb skeletal muscle, inguinal white adipose tissue (iWAT), and hearts were harvested and weighed. Lean body mass was assessed by analyzing the weight of the carcass following the excision of skin, subcutaneous fat, and visceral organs. Gene expression and protein levels in muscle tissues were subsequently quantified. Results: Phloretin administration significantly alleviated tumor-induced loss of tumor-free body weight. It effectively preserved skeletal muscle mass in both C26 and LLC cachexia models, while significantly attenuating adipose tissue depletion in the C26 model. In vitro, phloretin treatment mitigated myotube atrophy induced by C26 conditioned medium. Mechanistically, phloretin inhibited STAT3 activation in skeletal muscle. This inhibition suppressed the expression of the E3 ubiquitin ligases MuRF-1 and Atrogin-1. Furthermore, phloretin concurrently modulated the autophagy pathway. Conclusions: Phloretin effectively ameliorates cancer cachexia-induced muscle wasting by targeting STAT3-mediated protein degradation and autophagy pathways. These findings suggest that phloretin represents a promising therapeutic agent for the clinical management of cancer-associated cachexia. Full article

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains a leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) represent the two major histological subtypes with distinct molecular characteristics. POU domain class 6 transcription factor 1 (POU6F1) is involved in gene regulation and cellular differentiation, but its clinical significance in NSCLC remains unclear. This study investigated the clinicopathologic and prognostic significance of POU6F1 expression in NSCLC. POU6F1 mRNA expression was analyzed in tumor tissues obtained from 153 patients with NSCLC using quantitative real-time polymerase chain reaction. The associations between POU6F1 expression and clinicopathological characteristics were evaluated, and survival analysis was performed to determine its prognostic value. In addition, publicly available datasets from The Cancer Genome Atlas (TCGA) were analyzed to validate the clinical significance of POU6F1 expression. High POU6F1 expression was observed in 48 patients (31.4%), whereas 105 patients (68.6%) showed low expression. High POU6F1 expression was significantly associated with younger age (p = 0.027), female sex (p = 0.041), non-smoking status (p = 0.002), adenocarcinoma histology (p = 0.021), and the presence of EGFR mutations (p = 0.038). Survival analysis demonstrated that high POU6F1 expression was associated with improved overall survival in patients with NSCLC (p = 0.015). When stratified by histological subtype, higher POU6F1 expression was associated with better survival outcomes in AD but not in SCC. Analysis of TCGA datasets confirmed that elevated POU6F1 expression was significantly associated with favorable survival in AD, whereas no significant prognostic value was observed in SCC. POU6F1 expression is significantly associated with clinicopathological characteristics and improved survival in patients with lung AD. Multivariate Cox regression analysis further confirmed that POU6F1 expression was an independent prognostic factor for overall survival. These findings suggest that POU6F1 may serve as a potential prognostic biomarker based on mRNA expression in NSCLC, particularly in AD. Further studies are warranted to validate these findings at the protein level and to elucidate the underlying biological mechanisms. Full article

Background: Reliable biomarkers that capture tumor–host interactions and predict treatment resistance in extensive-stage small cell lung cancer (SCLC) remain limited. We evaluated the prognostic and predictive value of the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an integrative biomarker reflecting metabolic activity, systemic inflammation, and host nutritional status. Methods: This multicenter, retrospective cohort study included patients with extensive-stage SCLC treated at five tertiary centers between 2016 and 2024. Pretreatment LAR was calculated using baseline serum lactate dehydrogenase and albumin levels and dichotomized using a Youden index-derived cut-off at the 12-month overall survival (OS) horizon. Time-dependent receiver operating characteristic (ROC) analyses using inverse probability weighting were performed to assess discriminative performance. Survival outcomes were evaluated using Kaplan–Meier estimates and Cox proportional hazards models. Associations with platinum resistance and lack of objective treatment benefit (defined as progressive disease as best response) were examined using logistic regression models. Results: A total of 223 patients were included. Elevated LAR was associated with inferior OS (median, 15.8 vs. 25.2 months; log-rank p < 0.001) and progression-free survival (7.9 vs. 11.5 months; p < 0.001). In multivariable analysis, LAR remained independently associated with OS (HR, 1.43; 95% CI, 1.04–1.95; p = 0.028). LAR demonstrated modest but consistently superior discriminative performance compared with other inflammatory indices for both 12-month OS (area under the curve [AUC], 0.692) and 6-month progression-free survival (PFS) (AUC, 0.646), with statistically significant differences in DeLong comparisons. Higher LAR was independently associated with increased odds of platinum resistance (adjusted odds ratio [aOR], 2.31; 95% CI, 1.41–3.81; p = 0.001) and lack of objective treatment benefit (adjusted OR, 2.04; 95% CI, 1.33–3.14; p = 0.001). Conclusions: Pretreatment LAR is a clinically accessible and biologically integrative biomarker associated with survival and treatment resistance in extensive-stage SCLC. By capturing tumor–host interactions, LAR may support risk stratification and identify patients at increased risk of early treatment failure. Prospective validation is warranted to define its role in biomarker-driven clinical decision-making. Full article

Background: Tumor invasion is the central barrier to effective immunotherapy in lung adenocarcinoma (LUAD) and glioblastoma. Cell adhesion signaling critically shapes tumor–microenvironment interactions, yet the upstream regulators coordinating these invasive programs at single-cell resolution remain incompletely understood. Methyltransferase Like protein 7B (METTL7B) has recently emerged as a candidate oncogenic regulator, but its lineage-specific functions and the potential downstream effectors are unclear. Methods: We integrated publicly available single-cell RNA sequencing datasets from LUAD and glioblastoma with The Cancer Genome Atlas (TCGA) transcriptomic analyses to resolve METTL7B-associated malignant cell states and microenvironmental interactions. Functional enrichment analyses identified invasion- and focal adhesion pathways linked to METTL7B expression. Gain- and loss-of-function experiments were conducted in LUAD and glioblastoma cell lines to validate downstream cell adhesion effectors. Spatial expression patterns were examined using immunofluorescence, and transwell assays were used to assess migratory and invasive phenotypes. Results: Single-cell analyses revealed that METTL7B was selectively enriched in malignant epithelial cells in LUAD and glioblastoma and defined a transcriptional program characterized by cell adhesion signaling. Integrin Alpha 3 (ITGA3) emerged as a conserved downstream effector of METTL7B, with progressive upregulation from minimally invasive to invasive LUAD and glioblastoma. Functional perturbation confirmed that METTL7B enhances tumor cell migration and invasion through integrin-associated pathways. Conclusions: METTL7B acts as a potential lineage-enriched regulator of invasive tumor states by activating cell adhesion signaling in LUAD and glioblastoma. These findings position METTL7B as a putative prognostic factor for strategies aimed at limiting invasion in lung cancer and glioblastoma. Full article