Tumor Drug Research Articles

Exploring prognosis and therapeutic strategies for HBV-HCC patients based on disulfidptosis-related genes

BackgroundHepatocellular carcinoma (HCC) accounts for over 80% of primary liver cancers and is the third leading cause of cancer-related deaths worldwide. Hepatitis B virus (HBV) infection is the primary etiological factor. Disulfidptosis is a newly discovered form of regulated cell death. This study aims to develop a novel HBV-HCC prognostic signature related to disulfidptosis and explore potential therapeutic approaches through risk stratification based on disulfidptosis.MethodsTranscriptomic data from HBV-HCC patients were analyzed to identify BHDRGs. A prognostic model was established and validated using machine learning, with internal datasets and external datasets for verification. We then performed immune cell infiltration analysis, tumor microenvironment (TME) analysis, and immunotherapy-related analysis based on the prognostic signature. Besides, RT-qPCR and immunohistochemistry were conducted.ResultsA prognostic model was constructed using five genes (DLAT, STC2, POF1B, S100A9, and CPS1). A corresponding prognostic nomogram was developed based on riskScores, age, stage. Stratification by median risk score revealed a significant correlation between the prognostic signature and TME, tumor immune cell infiltration, immunotherapy efficacy, and drug sensitivity. The results of the experiments indicate that DLAT expression is higher in tumor tissues compared to adjacent tissues. DLAT expression is higher in HBV-HCC tumor tissues compared to normal tissues.ConclusionThis study stratifies HBV-HCC patients into distinct subgroups based on BHDRGs, establishing a prognostic model with significant implications for prognosis assessment, TME remodeling, and personalized therapy in HBV-HCC patients.

MRI-Based Multifunctional Nanoliposomes for Enhanced HCC Therapy and Diagnosis.

The morbidity and mortality rates of hepatocellular carcinoma (HCC) are high and continue to increase. The antitumor effects of single therapies are limited because of tumor heterogeneity and drug resistance, and the lack of real-time monitoring of tumor progression during the treatment process leads to poor therapeutic outcomes. Therefore, novel nanodelivery platforms combining tumor therapy and diagnosis have garnered extensive attention. In this study, we developed a multifunctional nanodelivery vector, LPSD-DOX/siRNA, which was loaded with oleic acid-modified superparamagnetic iron oxide nanoparticles (OA-SPION) and the antitumor drug doxorubicin (DOX), further modified by DOTAP to carry small interfering RNA targeting phosphatidylinositol proteoglycan-3 (Glypican-3, GPC3) (siRNA-GPC3). These components were utilized for the combined treatment of HCC and tumor monitoring with magnetic resonance imaging. LPSD-DOX/siRNA exhibited high drug loading, high gene transfection efficiency, and low toxicity. Pharmacokinetic and in vivo distribution experiments showed that LPSD-DOX/siRNA significantly prolonged the circulation time of DOX and enhanced drug accumulation at the tumor site. Magnetic resonance imaging demonstrated that LPSD-DOX/siRNA can serve as a T2 imaging contrast agent to enhance the imaging contrast between the tumor site and other tissues and facilitate the imaging monitoring of tumor tissues. Antitumor experiments revealed that the effects of DOX were promoted by inhibiting the expression of GPC3 protein in HepG2 cell-transplanted tumors, with increased tumor apoptosis. In conclusion, LPSD-DOX/siRNA serves as a promising strategy for combination therapy and monitoring of HCC, with significant potential in antitumor therapy.

Bioinformatics Analysis Reveals Microrchidia Family Genes as the Prognostic and Therapeutic Markers for Colorectal Cancer.

The aim of this study is to examine the role of the microrchidia (MORC) family, a group of chromatin remodeling proteins, as the therapeutic and prognostic markers for colorectal cancer (CRC). MORC protein family genes are a highly conserved nucleoprotein superfamily whose members share a common domain but have distinct biological functions. Previous studies have analyzed the roles of MORCs as epigenetic regulators and chromatin remodulators; however, the involvement of MORCs in the development and pathogenesis of CRC was less examined. The current work examined the role of the MORCs as the therapeutic and prognostic markers for CRC. The expressions and prognostic significance of MORC family genes in CRC were explored. The role of these genes in tumor immunity was comprehensively analyzed in terms of their functions in immune cell infiltration, tumor microenvironment (TME), and their interaction with immune regulatory genes such as immunosuppressive genes, immune checkpoints and immunostimulatory genes. The relations between MORC family genes, tumor mutation burden (TMB), DNA, mismatch repair (MMR), RNA methylation, microsatellite instability (MSI), and drug sensitivity were investigated using the R statistical software. The expressions of MORC4 in 150 CRC tissues and 60 paracancer tissues were detected by immunohistochemical method. CRC cell proliferation, migration, and invasion were measured by cell counting kit-8 (CCK-8), scratch assay, and transwell cell invasion assay. The expressions of MORC2 and MORC4 were significantly upregulated, whereas those of MORC1 and MORC3 were noticeably downregulated in CRC in comparison to their expressions in normal colorectal mucosal tissues. Patients with high-expressed MORC2 showed a more unfavorable prognosis than those with a low MORC2 level. Functional annotation analysis identified 100 MORC family genes with the most significant negative or positive correlations to diabetic cardiomyopathy, amyotrophic lateral sclerosis, oxidative phosphorylation, Huntington's disease, thermogenesis, Parkinson's disease, olfactory transduction, Alzheimer's disease, prion disease. MORC3 expression was positively correlated with Stromal score, Immune score and ESTIMATE score, while MORC2 expression was negatively related to the three scores in CRC, these correlations were not statistically significant. Additionally, the MORC family genes were significantly positively correlated with tumor-infiltrating immune cells such as T helper cells and exhibited close relations to some immunosuppressive genes such as CXCR4 and PVR, immunostimulatory genes such as TGFBR1, KDR, and CD160 as well as some immune checkpoint genes. It was found that the expressions of some members of MORC family genes were positively correlated with DNA methylation, MSI, TMB, MMRs, and drug sensitivity in CRC and that the mRNA and protein levels of MORC4 were remarkably upregulated in CRC tissues than in adjacent normal tissues (P<0.05). In the MORC4 knockdown group, DLD-1 cell proliferation was more inhibited than in the negative control (NC) and siRNA groups (P<0.05). Furthermore, the migratory capacity of DLD-1 cells and the number of cells crossing the basement membrane in the MORC4 knockdown group were reduced compared to the NC and siRNA groups (all P<0.05). The expressions of MORC family genes were significantly different in CRC samples, which was related to the immune cell infiltration and prognosis of CRC. Thus, the MORC family genes were considered as markers for indicating the clinical immunotherapy and prognostic outcome of CRC.

The regulatory role of integrin in gastric cancer tumor microenvironment and drug resistance.

Gastric cancer (GC) remains a significant global health burden due to its high aggressiveness, early metastasis, and poor prognosis. Despite advances in chemotherapy and targeted therapies, drug resistance remains a major obstacle to improving patient outcomes. Integrins, a family of transmembrane receptors, play a pivotal role in mediating tumor growth, invasion, and drug resistance by interacting with the tumor microenvironment (TME) and regulating signaling pathways such as Wnt/β-catenin, FAK, and MAPK. This review highlights the critical functions of various integrin subunits (e.g., α5, αv, β1, β3, β6) in promoting GC progression and their involvement in chemoresistance mechanisms. Additionally, integrins modulate immune cell infiltration and stromal cell interactions within the TME, further complicating GC treatment. Emerging evidence suggests that targeting integrins, either through inhibitors or integrin-specific therapeutic strategies, holds potential in overcoming drug resistance and improving clinical outcomes. This review underscores the need for further exploration of integrins as therapeutic targets in GC and suggests promising avenues for integrin-based therapies in personalized medicine.

First-line combination therapy of immunotherapy plus anti-angiogenic drug for thoracic SMARCA4-deficient undifferentiated tumors in AIDS: a case report and review of the literature

First-line combination therapy of immunotherapy plus anti-angiogenic drug for thoracic SMARCA4-deficient undifferentiated tumors in AIDS: a case report and review of the literature

Developing and validating a drug recommendation system based on tumor microenvironment and drug fingerprint

Developing and validating a drug recommendation system based on tumor microenvironment and drug fingerprint

Doxorubicin and topotecan resistance in ovarian cancer: Gene expression and microenvironment analysis in 2D and 3D models.

This study explores the mechanisms underlying chemotherapy resistance in ovarian cancer (OC) using doxorubicin (DOX) and topotecan (TOP)-resistant cell lines derived from the drug-sensitive A2780 ovarian cancer cell line. Both two-dimensional (2D) monolayer cell cultures and three-dimensional (3D) spheroid models were employed to examine the differential drug responses in these environments. The results revealed that 3D spheroids demonstrated significantly higher resistance to DOX and TOP than 2D cultures, suggesting a closer mimicry of in vivo tumour conditions. Molecular analyses identified overexpression of essential drug resistance-related genes, including MDR1 and BCRP, and extracellular matrix (ECM) components, such as MYOT and SPP1, which were more pronounced in resistant cell lines. MDR1 and BCRP overexpression contribute to chemotherapy resistance in OC by expelling drugs like DOX and TOP. Targeting these transporters with inhibitors or gene silencing could improve drug efficacy, making them key therapeutic targets to enhance treatment outcomes for drug-resistant OC. The study further showed that EMT-associated markers, including VIM, SNAIL1, and SNAIL2, were upregulated in the 3D spheroids, reflecting a more mesenchymal phenotype. These findings suggest that factors beyond gene expression, such as spheroid architecture, cell-cell interactions, and drug penetration, contribute to the enhanced resistance observed in 3D cultures. These results highlight the importance of 3D cell culture models for a more accurate representation of tumour drug resistance mechanisms in ovarian cancer, providing valuable insights for therapeutic development.

Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption.

The Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein and lipid sorting 1-5 . Dysregulation of its function has been implicated in various pathologies, including obesity, diabetes, and cancer, highlighting its importance as a potential therapeutic target. Despite this, the development of tools to selectively target the Golgi in specific cell types remain a significant unmet challenge in imaging and drug discovery. Golgi-specific enzyme activities, such as those mediated by protein acyltransferases and thioesterases 6 , offer an untapped opportunity to develop subcellularly localized therapeutics. Current approaches predominantly rely on direct protein binding but lack the necessary cell selectivity 7 , underscoring the unmet need for innovative strategies to selectively disrupt Golgi function in cancer cells. Here, we report the development of cycling molecular assemblies (CyMA), a novel class of small peptide derivatives (e.g., dipeptides), which exploit the unique enzymatic environment of the Golgi to establish futile cycles of reversible S-acylation. These assemblies selectively accumulate in cancer cell Golgi, interfering with protein S-acylation cycles and disrupting organelle homeostasis. CyMA impair key Golgi functions, including protein trafficking, glycosylation, and secretion, while demonstrating selective sparing hepatocytes and immune cells such as M1 macrophages. This selective activity represents a paradigm shift, utilizing an enzyme switch and leveraging intracellular environment rather than direct protein binding. Unlike conventional approaches, CyMA reduce tumor growth, drug resistance, and metastasis by pleiotropically disrupting Golgi related functions. By demonstrating the potential of futile cycles as a therapeutic strategy 8 , this study introduces a generalizable method for targeting organelle-specific enzyme activities. These findings not only underscore the therapeutic potential of CyMA in cancer but also pave the way for future applications in other Golgi-associated diseases.

Highly Sensitive Flow Cytometry Biosensor with a High Signal-to-Background Ratio for FEN1 Analysis via Solid-Phase Interface-Mediated Primer Exchange Reaction Amplification.

Flap endonuclease 1 (FEN1) is a specific enzyme capable of recognizing and cleaving triplex DNA structures and releasing 5'-flap fragments. It plays a crucial role in the DNA metabolism of cells, participating in DNA replication and the repair of damaged DNA. Additionally, FEN1 is overexpressed in various tumor tissues, promoting tumor progression and drug resistance through different regulatory mechanisms. However, few significant advancements have been made in sensitive analytical methods for detecting FEN1. Herein, in this study, we present a highly sensitive flow cytometry biosensor with solid-phase interface-mediated primer exchange reaction amplification (FCsperA) for FEN1 analysis. By comparing homogeneous PER amplification (h-PER), we found that solid-phase interface-mediated PER amplification (s-PER) effectively suppressed background signals, leading to a higher signal-to-background (S/B) ratio exceeding ∼46-fold when FEN1 was at 1 × 10-3 U/μL. Combining the high efficiency of s-PER, the strong suppression of background signals, and the highly precise flow cytometry assay, FCsperA showed high sensitivity, with a limit of detection (LOD) for FEN1 of 2.53 × 10-6 U/μL. Notably, FCsperA exhibited high selectivity and exceptional anti-interference ability, making it applicable for detecting FEN1 in cells and serum samples. The outstanding performance of FCsperA allowed for sensing FEN1 in ∼10 cancer cells. Additionally, FCsperA demonstrated the potential for screening inhibitors of FEN1.

Intelligent responsive nanogels: New Horizons in cancer therapy.

Biologically engineered nanogels formed through sophisticated intramolecular crosslinking processes represent the forefront of next-generation drug delivery systems. These innovative systems offer many advantages, like adjustable size, satisfactory biocompatibility, and minimal toxicity. Their unique attributes facilitate deep penetration and long-term retention of drugs in tumors, effectively enhancing the anti-tumor effects. Nonetheless, the rapid disintegration of nanogels and the subsequent triggering of drug release at the tumor site pose significant challenges in achieving more effective and precise tumor treatments. Therefore, increasing research has been dedicated to exploring stimulus-responsive nanogels for enhancing tumor therapy. This review aims to encapsulate the research advancements in emerging stimulus-responsive antitumor nanogels. Firstly, a detailed exposition is provided on various endogenous stimulus-responsive nanogels, encompassing factors such as pH, hypoxia, enzymes, reactive oxygen species (ROS), and glutathione (GSH). Secondly, various nanogels triggered by exogenous stimuli such as light, ultrasound, temperature, and magnetic fields are elaborately presented. Furthermore, nanogels with multifaceted stimulus-responsive properties are also skillfully designed. Finally, the future directions, application prospects, and challenges of intelligent responsive nanogels in cancer treatment are highlighted.

YY2-CYP51A1 signaling suppresses hepatocellular carcinoma progression by restraining de novo cholesterol biosynthesis.

Lipid accumulation is a frequently observed characteristic of cancer. Lipid accumulation is closely related to tumor progression, metastasis, and drug resistance; however, the mechanism underlying lipid metabolic reprogramming in tumor cells is not fully understood. Yin yang 2 (YY2) is a C2H2‑zinc finger transcription factor that exerts tumor-suppressive effects. However, its involvement in tumor cell lipid metabolic reprogramming remains unclear. In the present study, we identified YY2 as a novel regulator of cholesterol metabolism. We showed that YY2 suppressed cholesterol accumulation in hepatocellular carcinoma (HCC) cells by downregulating the transcriptional activity of cytochrome P450 family 51 subfamily A member 1 (CYP51A1), a key enzyme in de novo cholesterol biosynthesis. Subsequently, through in vitro and in vivo experiments, we demonstrated that this downregulation is crucial for the YY2 tumor suppressive effect. Together, our findings unraveled a previously unprecedented regulation of HCC cells cholesterol metabolism, and eventually, their tumorigenic potential, through YY2 negative regulation on CYP51A1 expression. This study revealed a novel regulatory mechanism of lipid metabolic reprogramming in tumor cells and provided insights into the molecular mechanism underlying the YY2 the suppressive effect. Furthermore, our findings suggest a potential antitumor therapeutic strategy targeting cholesterol metabolic reprogramming using YY2.

Role of vascular endothelium and exosomes in cancer progression and therapy (Review).

Cancer poses a significant global health challenge and its progression is intricately connected to the interplay among various cell types and molecular pathways. In recent years, research has focused on the roles of vascular endothelial cells (VECs) and exosomes within the tumor microenvironment. Anomalies in tumor vascular integrity and function create a conducive milieu for cancer cell proliferation. Despite efforts in clinical anti‑angiogenic interventions, the anticipated outcomes remain elusive. VECs have the capability to transition into mesenchymal cells through endothelial‑to‑mesenchymal transition, thereby affecting cancer advancement. Exosomes are minute membrane‑bound vesicles generated by cells, serving as vital extracellular elements that facilitate cell‑to‑cell communication. They participate in modulating the tumor microenvironment, thereby influencing tumor progression, metastasis, drug resistance and angiogenesis. Additionally, exosomes serve as efficient carriers for drug delivery, as well as targeting and suppressing tumor cells. In summary, understanding the intricate and interconnected mechanisms of VECs and exosomes in cancer, encompassing tumor angiogenesis, microenvironment modulation and immune regulation, is crucial. A comprehensive exploration of these mechanisms may provide insight into cancer treatment and prevention and yield novel therapeutic targets.

The Clinical Prediction Value of the Ubiquitination Model Reflecting the Microenvironment Infiltration and Drug Sensitivity in Breast Cancer.

The ubiquitin-proteasome system influences cancer progression through multiple mechanisms. Due to the extensive proteasomal modifications observed in cancer tissues, ubiquitination is closely related to various biological functions with cancer. However, the roles of ubiquitin-related genes (UbRGs) in breast cancer (BC) have not been thoroughly investigated. In this study, we retrieved 763 reliable UbRGs and identified a potential prognostic signature for breast cancer patients. Additionally, we analyzed eight overall survival-associated UbRGs using univariate Cox proportional hazard regression in the Cancer Genome Atlas (TCGA) database. Subsequently, we used Lasso-Cox risk regression analysis to generate prognostic characteristics of UbRGs associated with overall survival (OS), validated in an external cohort (GSE158309). Next, we compared differences in tumor microenvironment and drug sensitivity between subgroups, describing the potential impact of UbRGs on the landscape of the tumor immune microenvironment and their predictive significance for therapeutic resistance to different strategies. Furthermore, a nomogram model containing eight genes, histology, subtype, T status, N status, and the American Joint Committee on Cancer (AJCC) stage was constructed. Finally, in vitro and in vivo experiments validated the effects of FBXL6 and PDZRN3 on breast cancer development. In conclusion, we demonstrate that ubiquitin-related genes are closely associated with breast cancer prognosis, immune environment, and drug sensitivity. Our results offer a new insight into breast cancer treatment.

Incorporation of a rigid 1,3-diketone-containing fragment led to significantly improved AXL inhibitory activity: design, synthesis, and SAR of the anilinopyrimidine AXL inhibitors.

Overexpressed AXL kinase is involved in various human malignancies, which incurs tumor progression, poor prognosis, and drug resistance. Suppression of the aberrant AXL axis with genetic tools or small-molecule inhibitors has achieved valid antitumor efficacies in both preclinical studies and clinical antitumor campaigns. Herein we will report the design, synthesis, and structure-activity relationship (SAR) exploration of a series of anilinopyrimidine type II AXL inhibitors. Among these inhibitors, 4l exhibited the enzymatic AXL and cellular BaF3/TEL-AXL IC50 values of 0.5nM and less than 0.2nM, respectively. Western blot analysis displayed that 4l dose-dependently inhibited the phosphorylation of AXL and its downstream cascade Akt, which was better than that of the reference control R428. Moreover, 4l markedly suppressed the AXL/GAS6-mediated migration in NCI-H1299 cells.

Effective Targeting of Glutamine Synthetase with Amino Acid Analogs as a Novel Therapeutic Approach in Breast Cancer

Cancer cells undergo metabolic rewiring to support rapid proliferation and survival in challenging environments. Glutamine is a preferred resource for cancer metabolism, as it provides both carbon and nitrogen for cellular biogenesis. Recent studies suggest the potential anticancer activity of amino acid analogs. Some of these analogs disrupt cellular nucleotide synthesis, thereby inhibiting the formation of DNA and RNA in cancer cells. In the present study, we investigated the anticancer properties of Acivicin and Azaserine in the breast cancer MCF-7 cell line, comparing their effects to those on the non-tumorigenic MCF-10 epithelial cell line in vitro. Interestingly, at lower concentrations, both Acivicin and Azaserine showed potent inhibition of MCF-7 cell proliferation, as assessed by the MTT assay, without detectable toxicity to normal cells. In contrast, Sorafenib (Nexavar), a commonly used drug for solid tumors, showed harmful effects on normal cells, as indicated by increased lactate dehydrogenase (LDH) production in treated cells. Furthermore, unlike Sorafenib, treatment with Acivicin and Azaserine significantly affected apoptotic signaling in treated cells, indicating the role of both amino acid analogs in activating programmed cell death (PCD), as assessed by the Annexin-V assay, DAPI staining, and the relative expression of tumor suppressor genes PTEN and P53. ELISA analysis of MCF-7 cells revealed that both Acivicin and Azaserine treatments promoted the production of anti-inflammatory cytokines, including IL-4 and IL-10, while significantly reducing the production of tumor necrosis factor alpha (TNF-α). Mechanistically, both Acivicin and Azaserine treatment led to a significant reduction in the expression of glutamine synthetase (GS) at both the RNA and protein levels, resulting in a decrease in intracellular glutamine concentrations over time. Additionally, both treatments showed comparable effects on Raf-1 gene expression and protein phosphorylation when compared with Sorafenib, a Raf-1 inhibitor. Moreover, docking studies confirmed the strong binding affinity between Acivicin, Azaserine, and glutamine synthetase, as evidenced by their docking scores and binding interactions with the enzyme crystal. Collectively, these findings provide evidence for the anticancer activity of the two amino acid analogs Acivicin and Azaserine as antagonists of glutamine synthetase, offering novel insights into potential therapeutic strategies for breast cancer.

Progress in Structural Modification and Anti-Tumor Activity of Plant Polysaccharides: Enhancing Efficacy and Bioavailability

Plant polysaccharides are a class of widely distributed biomolecules with significant and diverse bioactivities, such as anti-tumor, anti-inflammatory, antioxidant, antimicrobial and immunoregulation, making them promising candidates for anti-tumor biopharmaceuticals. In this review, recent advancements in the anti-tumor research of plant polysaccharides are summarized from three perspectives: the inherent anti-tumor activity of plant polysaccharides, the enhancement of this activity through chemical modifications, and the development of polysaccharide-based drug delivery systems. Chemical modifications, especially sulfation, phosphorylation, acetylation, and carboxymethylation, have been shown to significantly enhance the antitumor efficacy of plant polysaccharides by promoting apoptosis and modulating immune responses. Furthermore, polysaccharide-based drug delivery systems have been proven effective in reducing tumor drug resistance and improving bioavailability. Based on these findings, we propose two key directions for future research: first, translating these advancements into clinical applications to benefit patients, and second, deepening interdisciplinary research to further enhance our understanding and application of plant polysaccharides in cancer therapy.

Application of Immunotherapy in the Treatment of Solid Tumors

Cancer is one of the major diseases that seriously threaten human life and health at present, and the number of deaths due to cancer every year ranks in the top 2 of all diseases. In recent years, the malignant tumor is increasing year by year, so it is necessary to explore new therapeutic methods. Immunotherapy of tumor cells is one of the hot topics in tumor therapy, which aims to destroy tumor cells by activating or regulating the immune system of patients. More and more tumor immunotherapy drugs have been successfully developed and marketed, bringing the hope of long-term survival to patients. However, like other tumor drug therapy, tumor immunotherapy has brought huge benefits to some tumor patients and made people full of expectations, but it also faces many difficulties and challenges in pre-clinical research and clinical application. This article summarizes the application and challenge of immunotherapy in solid tumors.

A Miniaturized In Vivo Fluorescence Microscopy Method for Monitoring Circulating Tumor Cells in Freely Moving Animals

ABSTRACTMetastasis is the leading cause of death in tumor patients, with circulating tumor cells (CTCs) serving as key biomarkers for tumor progression, metastasis, and recurrence. CTC quantity is closely linked to tumor dynamics, which are influenced by biological rhythms. Studying CTC distribution under various physiological conditions provides insights into metastasis mechanisms. However, due to the low abundance of CTCs, detection accuracy is limited, especially with small blood samples, making continuous data collection challenging. To address this, we developed a dual‐channel miniaturized in vivo fluorescence microscopy system for real‐time monitoring of CTCs in experimental animals. This system, which can be fixed to the head or back, enables dynamic, quantitative analysis of CTCs in the circulatory system. It offers a valuable tool for investigating tumor metastasis rhythms, drug evaluation, and prognostic assessment in freely moving animals, advancing research in metastasis mechanisms and cancer treatment.

Programmed cell death pathways in lung adenocarcinoma: illuminating tumor drug resistance and therapeutic opportunities through single-cell analysis.

Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell death (PCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, in shaping LUAD heterogeneity, immune infiltration, and prognosis. Among these, ferroptosis and pyroptosis were most significantly associated with favorable survival outcomes, highlighting their potential roles in enhancing anti-tumor immunity. Distinct PCD-related LUAD subtypes were identified, characterized by differential pathway activation and immune cell composition. Subtypes enriched with cytotoxic lymphocytes and dendritic cells demonstrated improved survival outcomes and increased potential responsiveness to immunotherapy. Drug sensitivity analysis revealed that these subtypes exhibited heightened sensitivity to targeted therapies and immune checkpoint inhibitors, suggesting opportunities for personalized treatment strategies. Our findings emphasize the interplay between PCD pathways and the tumor microenvironment, providing insights into the mechanisms underlying tumor drug resistance and immune evasion. By linking molecular and immune features to clinical outcomes, this study highlights the potential of targeting PCD pathways to enhance therapeutic efficacy and overcome resistance in LUAD. These results contribute to a growing framework for developing precise and adaptable cancer therapies tailored to specific tumor characteristics.

Exosomal long non-coding RNAs in lung cancer: A review.

Lung cancer is one of the most threatening malignancies among the different kinds of tumors. The incidence and mortality rate are increasing especially in male. Advances in diagnosis and treatment have been achieve in recent years. However, the lung tumor cells also developing chemo- and radio-resistance. Novel approaches and new treatments are stilled needed to develop for early diagnosis and treatment. Recently, long non-coding RNAs (lncRNAs) original exosomes were proved different expression in lung tumor, which mediate multiple biological processes and is responsible for tumor proliferation and metastasis. In this review, we focus on the emerging roles of both lncRNAs and exosomal lncRNAs in lung cancer and their roles on angiogenesis, metastasis, diagnosis, drug resistance, and immune regulation of lung cancer. Exosome lncRNAs were proved to serve as regulatory factors for gene expression, mediating intercellular communication, and participating in the occurrence and development of various diseases. In addition, exosomes lnc RNA has advantages on the early diagnosis of lung cancer, tumor cell metastasis, drug resistance, and immune regulation. Exosome lncRNAs an provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future.