ObjectiveTo explore the role of chloride intracellular channel 5 (CLIC5) in the development of lung adenocarcinoma (LUAD). MethodsThe expression levels of CLIC5 in LUAD samples were determined using bioinformatics and qRT-PCR. The correlation between CLIC5 expression and LUAD progression was revealed through survival analysis and clinicopathological feature analysis. After the knockdown or overexpression of CLIC5 in the LUAD cells, cell proliferation was assessed through colony formation assay, cell apoptosis rate by flow cytometry, and cell migration and invasion by scratch and Transwell invasion assay. The protein levels of vimentin and Snail were detected by Western blot. ResultsBioinformatics analysis results showed low CLIC5 expression levels in the LUAD samples. This finding was associated with the aggressive progression of LUAD and the poor survival of patients with LUAD. The qRT-PCR results confirmed that CLIC5 was mainly expressed in the cytoplasm of the LUAD cells. CLIC5 overexpression inhibited cell activity and proliferation and promoted the apoptosis of LUAD cells. The knockdown of CLIC5 exhibited the opposite effect. CLIC5 overexpression inhibited the migration and invasion of LUAD cells, downregulated Bcl-2, vimentin, and Snail and upregulated Bax, cleaved caspase-3 and E-cadherin in the LUAD cells. CLIC5 knockdown exhibited opposite effects. ConclusionCLIC5 overexpression promotes cell apoptosis and inhibits cell proliferation and invasion, thereby inhibiting the development of LUAD. Hence, CLIC5 is a novel biomarker of prognosis and therapeutic target for LUAD.
Objective To explore the correlation between alterations in intestinal microbiota composition and abnormal cytokine expression in patients with gastric cancer.Methods Fecal and peripheral blood samples were collected from 81 patients with gastric cancer(gastric cancer group)and 85 healthy subjects(healthy control group).Fecal bacterial DNA was sequenced through 16S rRNA gene amplicon sequencing,and the serum levels of 17 cytokines were measured with the AimPlex multiplex assay technology:IL-1β,IL-2,IL-4,IL-6,IL-8,IL-10,IL-12p70,IL-15,IL-17A,TNF-α,TNF-β,GM-CSF,G-CSF,IFN-γ,IP-10,MCP-1,and VEGF-A.Results In the gastric cancer group,the abundances of 11 butyrate-producing bacteria,including certain genera of the Lachnospiraceae family(such as Lachnospira and Roseburia)and Faecalibacterium,considerably decreased.By contrast,the abundances of nine bacterial taxa,including Escherichia-Shigella,Streptococcus,Veillonella,and Parabacteroides,significantly increased.Correlation analysis showed that the decrease in the abundance of butyrate-producing bacteria were significantly negatively correlated with the high expression levels of pro-angiogenic and immunosuppressive cytokines in the gastric cancer group,including IP-10,IL-10,MCP-1,IL-8,IL-6,and VEGF-A.However,the decrease was significantly positively correlated with the downregulation of antitumor immune-related cytokines,including IL-2,IL-17A,IL-1β,TNF-β,and GM-CSF.Conversely,the enriched bacterial taxa exhibited opposite correlation patterns with these cytokines.Conclusion A close correlation is observed between intestinal microbiota dysbiosis and abnormal cytokine expression in patients with gastric cancer.The findings suggest that restoring the intestinal microbiota through fecal microbiota transplantation is a promising strategy for regulating cytokines and is a potential research direction for the adjuvant therapy of gastric cancer.
Objective To investigate the causal relationship between immune cells and various molecular subtypes of breast cancer(BC)by using two-sample Mendelian randomization(MR).Methods This study employed a two-sample MR analysis,with 731 immune cell types from the GWAS catalog as the exposure factors and four BC molecular subtypes(HR+/HER2-,HR+/HER2+,HR-/HER2+,and HR-/HER2-)from the BCAC Consortium as the outcome variables.For causal inference,inverse variance weighting(IVW)was employed as the primary analytical method,alongside multiple consistency validation approaches,including MR-Egger,weighted median,weighted mode,simple mode,and Bayesian weighted Mendelian randomization.Reverse MR and sensitivity analyses were employed to effectively evaluate and exclude potential biases and interference from reverse causality.Results Significant causal associations were identified for specific immune cell phenotypes across subtypes.In HR+BC,the HER2+subtype was associated with seven immunophenotypes(five protective and two risk increasing),whereas the HER2-subtype was associated with eight immunophenotypes(four protective and four risk increasing).In HR-BC,the HER2+subtype was associated with five immunophenotypes(one protective and four risk increasing),and the HER2-subtype(triple-negative BC)was associated with seven immunophenotypes(six protective and one risk-increasing).CD28+CD45RA-CD8+T cells and naive CD8+T cells have a bidirectional causal relationship with HR+/HER2+breast cancer,Whereas the expression of CD8 on CD39+CD8+cells also has a bidirectional relationship with HR+/HER2-breast cancer.Furthermore,CD4-CD8-NKT cells exhibited opposing effect directions in HER2+versus HER2-subtypes.Conclusion From a genetic perspective,this study confirms the existence of subtype-specific causal associations between immune cell phenotypes and distinct molecular subtypes of BC,revealing heterogeneity in immune regulation.
Chimeric antigen receptor T-cell (CAR-T) therapy, a revolutionary technology in tumor immunotherapy, has achieved breakthrough progress in the treatment of hematological malignancies. To date, multiple CAR-T products have been approved for clinical use worldwide, but progress in their application to solid tumor treatment has been slow mainly due to the highly complex biological characteristics of solid tumors. In recent years, the continuous identification of novel targets in solid tumors, continuous innovations in genetic engineering technologies, growing maturity of combination therapeutic strategies, and rapid advancement in artificial intelligence have expanded the potential applications of CAR-T therapy in solid tumor treatment, highlighting its broad translational prospects. This article systematically reviews recent clinical progress in CAR-T therapy for solid tumors, comprehensively analyzes core challenges and corresponding countermeasures, and outlines future directions.
Colorectal cancer (CRC) is a common malignant tumor. The treatment of patients with advanced disease still faces severe challenges. Among patients with metastatic colorectal cancer (mCRC), most of those with microsatellite stable (MSS)/proficient mismatch repair (pMMR) tumors are highly insensitive to monotherapy with immune checkpoint inhibitors. With in-depth investigations into the mechanisms of the tumor immune microenvironment in MSS/pMMR CRC, the combination strategies of immunotherapy and targeted therapy have become a key direction to break through the treatment bottleneck in this population. These strategies include combinations of immunotherapy with antiangiogenic agents, epidermal growth factor receptor inhibitors, histone deacetylase inhibitors, and MAPK pathway inhibitors. Although the current relevant evidence is mainly derived from early-phase clinical trials, a number of studies demonstrated that immunotherapy combined with targeted therapy can improve the objective response rate and survival benefit in patients with MSS/pMMR mCRC and shows remarkable efficacy advantages in specific subgroups. This article systematically reviews the biological basis and clinical research progress of relevant combination therapeutic strategies, discusses potential beneficiary subgroups, and prospects future research directions. It aims to provide theoretical evidence and clinical references for optimizing the individualized treatment paradigm for this large patient population.
Hereditary carotid body tumor (HCBT) is a rare neuroendocrine tumor mainly caused by germline mutations of the SDHx gene. Its multifocality, familial aggregation, and potential malignant risk pose unique challenges to diagnosis and treatment. This review systematically expounds the molecular mechanism of HCBT, pointing out that SDHx mutations drive tumorigenesis through the “pseudo-hypoxia” pathway and are regulated by epigenetic and somatic mutations. In terms of diagnosis, we emphasize the crucial role of 68Ga-DOTATATE PET/CT and SDHB immunohistochemistry and advocate for multigene panel sequencing for patients with high-risk characteristics (such as early-onset, multifocal, family history or malignant signs) to clarify the genetic background. On the basis of existing evidence, we recommend conducting baseline biochemical tests for all newly diagnosed patients and actively suggest genetic screening for high-risk individuals such as those who are young, have multifocal tumors, or have a family history. In terms of treatment, surgery is the main treatment method for HCBT. Nevertheless, individualized strategies still need to be formulated based on tumor classification and patient’s overall condition and genetic background. Comprehensive management measures such as targeted therapy, radionuclide therapy, and standardized family management are crucial for improving the prognosis of patients.
Hyperthermic intrathoracic chemotherapy (HITHOC) is a localized treatment that combines hyperthermia with medications such as chemotherapy, anti-angiogenic agents, targeted therapy, or immunotherapeutic agents. It has advanced clinical progress for conditions such as malignant pleural mesothelioma, pleural metastasis of lung cancer, and pleural dissemination of thymic tumors. Systematic analyses indicate that as an adjuvant therapy to cytoreductive surgery, HITHOC improves patient survival and effectively controls pleural effusion and pleural metastasis. It exerts antitumor effects by enhancing drug penetration through thermal effects, inducing apoptosis, and modulating the immune microenvironment. HITHOC combined with systemic therapies (e.g., chemotherapy, targeted therapy, and immunotherapy) demonstrates synergistic potential, but its role as a local treatment should be clearly defined as adjunctive within the comprehensive management of advanced-stage patients. Further research is needed to clarify its indications, standardized protocols, and long-term efficacy and to explore optimized regimens and personalized combination treatment strategies. This review delves into the key bottlenecks hindering the development of hyperthermia therapy, such as the lack of high-level evidence-based medicine and the absence of standardized diagnostic and efficacy evaluation criteria, and proposes potential solutions.
ObjectiveTo investigate the expression characteristics, prognostic value, and correlation with immune infiltration of vasoactive intestinal peptide receptor 2 (VIPR2) in esophageal adenocarcinoma (ESAD). MethodsTranscriptome data of 80 ESAD and 10 normal tissues were retrieved from the TCGA database. Immune-related differential genes were identified by integrating the ImmPort database. Cox regression analysis was applied to evaluate the prognostic significance of VIPR2. GSVA and ssGSEA were employed to assess the association between VIPR2 and immune-cell infiltration. Functional enrichment was performed using GO, KEGG, and GSEA. ResultsVIPR2 expression was significantly downregulated in ESAD tissues (P<0.05). High VIPR2 expression was associated with prolonged overall survival (HR=0.246, P=0.047), serving as an independent prognostic factor. Fifteen immune-cell types, including CD8+ T cells, NK cells, and dendritic cells, showed significantly higher infiltration in the VIPR2-high group, whereas Th17-cell abundance was decreased (P<0.05). Enrichment analyses revealed that VIPR2 participated in multiple tumor-immune pathways and was positively correlated with PD-1 and CTLA-4 expression (P<0.01). ConclusionVIPR2 may serve as a potential biomarker in the prognostic assessment and could modulate the tumor-immune microenvironment in ESAD.
ObjectiveTo analyze the factors affecting the prognosis of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) undergoing immunotherapy and construct an individualized prognostic nomogram prediction model. MethodsA retrospective analysis was conducted on the clinical data of 385 patients with driver gene-negative, locally advanced or metastatic NSCLC who received first-line immune checkpoint inhibitors. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors, and a prognostic nomogram model was established. The predictive performance of the model was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves and area under the curve (AUC), and calibration curves. The cutoff value of the nomogram was calculated to stratify patients by risk. Survival curves were calculated by Kaplan-Meier analysis. ResultsAge (HR=1.775, 95%CI: 1.265-2.490), degree of differentiation (HR=0.365, 95%CI: 0.257-0.519), low PD-L1 expression (HR=0.661, 95%CI: 0.455-0.960), high PD-L1 expression (HR=0.423, 95%CI: 0.297-0.603), SCC-Ag (HR=1.549, 95%CI: 1.109-2.163), and CONUT score (HR=2.527, 95%CI: 1.797-3.554) were independent risk factors affecting overall survival (OS) of patients with NSCLC undergoing immunotherapy. The nomogram prediction model constructed on the basis of these factors had a C-index of 0.767. Time-dependent ROC curves for survival showed that the AUCs for 1-, 2-, and 3-year OS were 0.830, 0.853, and 0.886, respectively. Calibration curves indicated that the nomogram-predicted survival rates were in good agreement with the actual outcomes. The cutoff value for the study’s nomogram prediction model was 136.60 points, and survival curves showed statistically significant differences between different risk groups (P<0.05). ConclusionThe nomogram model established in this study can effectively predict the prognosis of patients with driver gene-negative locally advanced or metastatic NSCLC treated with first-line immunosuppressive therapy. It provides a new tool for assessing prognosis and aids clinicians in formulating individualized treatment plans.
Objective To evaluate the association between paroxetine exposure and breast cancer risk by using a multi-omics approach and to elucidate the underlying molecular mechanisms.Methods A cross-sectional analysis was conducted using NHANES data from 2005 to 2016 to assess paroxetine exposure and breast cancer prevalence.Network pharmacology was employed to identify common targets and pathways,followed by Mendelian randomization analysis to validate causal relationships and molecular docking to further verify key interactions.Results Among 5 520 participants,paroxetine users showed a 270％increased risk of breast cancer after multivariate adjustment(adjusted OR=3.70,95％CI:1.15-11.99,P=0.032).Network pharmacology identified 92 overlapping targets,with mTOR emerging as a central hub(IVW OR=1.09,95％CI:1.06-1.13,P=6.67×10-7).Molecular docking confirmed a high-affinity binding between paroxetine and mTOR(binding energy:-8.3 kcal/mol).Pathway enrichment analysis indicated that the PI3K-Akt signaling pathway,endocrine resistance,and chemical carcinogenesis were key mechanisms.Conclusion Paroxetine use may be linked to an increased risk of breast cancer,possibly mediated through the mTOR pathway.
ObjectiveTo explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. MethodsA cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. ResultsThe prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. ConclusionDepression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.
Bladder tumor is a common tumor in the urinary system, posing a serious threat to patients’ health and quality of life. The standard surgical method for non-muscle-invasive bladder cancer is the transurethral resection of bladder tumor. As a new type of minimally invasive treatment, transurethral holmium laser has shown unique advantages in the treatment of bladder tumors. This work introduces the epidemiological characteristics of bladder tumors and the limitations of traditional treatment methods and elaborates on the technical principles, development history of holmium laser and its application status in the treatment of bladder tumors. By analyzing clinical research data, it compares therapeutic effects between holmium laser and other treatment methods. It also presents the key points of surgical techniques, perioperative management strategies, and measures for the prevention and treatment of complications. This research discusses the current technical challenges and future development directions in holmium laser treatment, providing references for clinical practice and research.
ObjectiveTo summarize the clinical characteristics and analyze prognostic factors of neuroblastoma (NB) in infants (≤12 months) at a single center. MethodsA retrospective analysis was conducted on the clinical data of infant patients (≤12 months) diagnosed with NB and treated between January 2014 and December 2022. Clinical features were analyzed, and comparisons between two sample rates were performed using the χ2 test. Univariate prognostic analysis was conducted using the log-rank test, and survival outcomes were analyzed using the Kaplan-Meier method. ResultsA total of 42 infants (≤12 months) with NB were enrolled. Low-risk patients underwent surgical resection alone; intermediate-risk patients received surgery combined with chemotherapy with or without maintenance therapy; high-risk patients were treated with surgery and chemotherapy with or without maintenance therapy or radiotherapy. The 5-year event-free survival (EFS) rate was (92.7±4.9)%, and the 5-year overall survival rate was (95.2±3.6)%. Only two patients died because of tumor recurrence or progression. Univariate analysis identified MYCN amplification and the initial lactate dehydrogenase (LDH) level ≥ five times the upper limit of the normal were significantly associated with poor prognosis (5-year EFS: 33.3% vs. 97.4% and 60.0% vs. 97.3%, P<0.0001 and P=0.0035). ConclusionInfant NB has a favorable overall prognosis. MYCN amplification and markedly elevated initial LDH are associated with poor outcomes.
Antibody-drug conjugates (ADCs) have emerged as a standard treatment modality for previously treated driver gene-positive advanced non-small cell lung cancer (NSCLC). Sacituzumab tirumotecan (sac-TMT), a novel TROP-2-targeting ADC, has been the focus of the phase Ⅲ clinical trial OptiTROP-Lung04. This trial demonstrated, for the first time, that single-agent sac-TMT significantly improves progression-free survival and overall survival compared with conventional platinum-based chemotherapy in patients with epidermal growth factor receptor (EGFR) mutant advanced NSCLC following resistance to EGFR tyrosine kinase inhibitors. This review combines existing consensus from literature with the latest research evidence to systematically analyze OptiTROP-Lung04 from multiple perspectives, including molecular mechanisms, study design, clinical significance, and safety management. Furthermore, it explores future development directions in an effort to provide new insights into precision therapy for advanced NSCLC.
一、概述 据中国国家癌症中心发布的数据,2022年全国原发性肝癌发病人数36.77万,占全球病例的42.5％,位列各种癌症新发患者数第4位、发病率位列第5位;2022年因原发性肝癌死亡人数31.65万,死亡人数和病死率均位列第2位;人群肝癌5年相对生存率为14.4％,诊断时为中期和晚期比例达50％以上[1-3].原发性肝癌主要包括肝细胞癌(hepatocellular carcinoma,HCC)、肝内胆管癌(intrahepatic cholang-iocarcinoma,ICC)和混合型肝细胞癌-胆管癌(comb-ined hepatocellular-cholangiocarcinoma,cHCC-CCA)三种不同病理学类型,三者在发病机制、生物学行为、病理组织学、治疗方法以及预后等方面差异较大,其中HCC占80％、ICC占14.9％[4].本指南中的"肝癌"仅指HCC.
ObjectiveTo establish an epirubicin (EPI)-resistant murine triple-negative breast cancer (TNBC) (4T1/EPI) cell line and evaluate its biological characteristics and drug resistance. MethodsThe EPI-resistant cell line 4T1/EPI was developed through intermittent induction with gradually increasing EPI concentrations in vitro. Morphological changes were observed under an inverted microscope. Drug resistance index (MTT assay), cell doubling time (CCK-8 assay), and migration ability (wound healing assay) were evaluated. Western blot was used to detect the expression of drug resistance-related proteins. Transcriptome sequencing and KEGG pathway enrichment analysis were performed to identify the pathways and targets involved in EPI resistance, followed by experimental validation. ResultsThe 4T1 cells eventually grew normally in a medium containing 100 ng/mL EPI, confirming the establishment of the 4T1/EPI resistant cell line. After stable resistance was acquired, morphological alterations were observed. Compared with their parental 4T1 cells, 4T1/EPI cells showed significantly prolonged doubling time (P<0.01) and enhanced migration ability (P<0.05). Expression levels of drug resistance-related proteins MDR1, MRP1 (P<0.01), and ABCG2 (P<0.05) were elevated in 4T1/EPI cells. In vivo models also demonstrated significant EPI resistance in 4T1/EPI tumors in terms of tumor weight and volume. Transcriptome sequencing highlighted the involvement of the PI3K/Akt signaling pathway and ABC transporter pathway. Validation experiments showed the upregulation of Erbb3, Egfr, PI3K, and Akt (P<0.05) and significant downregulation of Fgfr1 (P<0.01) in 4T1/EPI cells. ConclusionThe EPI-resistant TNBC cell line 4T1/EPI was successfully established, exhibiting significant resistance in vitro and in vivo. The mechanism may involve the EPI-induced upregulation of Egfr and Erbb3, activating the PI3K/Akt pathway and subsequently enhancing ABC transporter expression.
ObjectiveTo investigate the expression of CPEB2 in triple-negative breast cancer (TNBC) and its impact on the malignant progression of tumors. MethodsThe expression level of CPEB2 in breast cancer was analyzed through a database, and the differential expression in clinical pathological specimens was verified by immunohistochemical experiments. Stable CPEB2 overexpressing TNBC cell lines were constructed, and CCK-8 and Transwell assays were used to detect the changes in cell phenotypes. Western blot was used to explore the expression of key molecules in the MEK/ERK signaling pathway. ResultsThe expression of CPEB2 in TNBC tissues was significantly lower than that in adjacent tissues (χ2=16.57, P<0.001). Patients with high expression of CPEB2 had a significantly longer overall survival than those with low expression. Overexpression of CPEB2 inhibited the proliferation, migration, and invasion abilities of TNBC cells and the activation of the MEK/ERK signaling pathway. ConclusionThe expression of CPEB2 is downregulated in TNBC. Upregulation of CPEB2 inhibits the proliferation, migration, and invasion of TNBC cells, accompanied by decreased activation of the MEK/ERK pathway (reduced p-MEK and p-ERK levels), suggesting that CPEB2 may participate in the malignant progression of TNBC by regulating the MEK/ERK pathway.
Casein kinase 2-interacting protein-1 (CKIP-1) is a multifunctional scaffold protein with a pleckstrin homology domain. Its dynamic subcellular localization enables dual roles in tumor progression, “promoting” or “suppressing” malignancy by regulating immune metabolism and signaling networks within the tumor immune microenvironment (TIME). This review synthesizes current knowledge on CKIP-1’s structural characteristics and TIME regulatory mechanisms. We highlight that CKIP-1 inhibits macrophage M2 polarization, antagonizes Smurf1-mediated oncoprotein ubiquitination, and modulates key pathways, including TGF-β and PI3K/AKT. Targeting CKIP-1 enhances the efficacy of immune checkpoint inhibitors and CAR-T therapy, but clinical translation faces challenges, such as unclear tissue-specific mechanisms and combination toxicity. This review aims to synthesize the regulatory functions of CKIP-1 in the tumor immune microenvironment, thereby offering a theoretical basis for precision immunotherapy targeting CKIP-1 and further analyzing its dynamic mechanisms to advance clinical applications.
Acute myeloid leukemia (AML) is characterized by marked biological heterogeneity, and molecular classification is essential for therapeutic decision-making and prognostic stratification. With the advancement of precision oncology, genotype-directed targeted therapy has emerged as a critical element in the management of AML. Although KMT2A rearrangements and NPM1 mutations arise from distinct molecular events, both converge on aberrant activation of the HOX/MEIS1 transcriptional program, thereby sustaining the self-renewal of leukemic stem/progenitor cells and impairing myeloid differentiation to promote leukemogenesis and disease progression. Menin, encoded by the tumor suppressor gene MEN1, functions as a nuclear scaffold protein and serves as an essential mediator for the assembly of KMT2A fusion-driven transcriptional complexes, recruitment of cooperative cofactors, and stabilization of oncogenic transcriptional networks. The disruption of the Menin-KMT2A interaction represents a mechanistically grounded therapeutic strategy. In recent years, multiple Menin inhibitors have progressed to clinical development and exhibited clinically significant activity in AML subsets with KMT2A rearrangements or NPM1 mutations. This review summarizes current progress in the research and clinical application of Menin inhibitors in AML, focusing on pharmacological mechanisms, efficacy and safety profiles derived from clinical studies, and emerging resistance mechanisms, including recurrent MEN1 hotspot mutations and epigenetic/transcriptional reprogramming. We further discuss rational combination approaches and directions for the development of next-generation agents, aiming to enhance clinical practice and guide future research.
The spine is the most common site of skeletal metastasis in lung cancer, which frequently leads to severe complications such as pathological fracture and neurological compromise and is associated with poor prognosis. The development and progression of spinal metastasis from lung cancer are linked to the unique local microenvironment and tumor microenvironment (TME) of the vertebral column. During metastatic evolution, the dense vascular network of the spine and a plethora of signaling molecules, together with the complex cellular constituents and their intricate interactions within the TME, all cooperate to facilitate the tumor invasion and colonization of the vertebral compartment. Mechanistic studies delineating the role of the TME in spinal metastasis from lung cancer have markedly expanded, fostering the emergence of innovative therapeutic strategies—including nanomedicines, sono-photodynamic therapy, gene therapy, and combination regimens. These strategies demonstrate remarkably potential for clinical translation and offer new directions for the precision management of spinal metastasis from lung cancer.
