Strategy For Lung Cancer Research Articles

Frequency of EGFR mutation and EML4-ALK fusion genes in patients with non-small cell lung carcinoma

Lung cancer ranks among the top causes of mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for the majority of cases. Advances in genomics have identified potential biomarkers to predict therapeutic strategies in lung cancer. Despite the availability of targeted drugs such as tyrosine kinase inhibitors, a substantial proportion of patients still experience problems such as drug resistance. Mutations in genes like epidermal growth factor receptor (EGFR) and EML4ALK have already been established with altered clinical outcomes in NSCLC patients. With a focus on non-small cell lung cancer (NSCLC),the study was conducted at indraprastha apollo hospital in new delhi. With their informed agreement, 90 patients who were admitted between january 2012 and december 2015 and who had been diagnosed with fine-needle aspiration cytology (FNAC)/biopsy utilizing computed tomography (CT) guidance were included in the study. Excluded from the study were those receiving radiation therapy or chemotherapy concurrently. Information on age, gender, a thorough medical history, a history of smoking, and any additional co-morbidities were taken from medical records. Investigation of EGFR mutation and EML4-ALK gene fusion in NSCLC patients was done. Eleven (11% ) were positive and (89%) were negative for EGFR mutations. The positive cases were analyzed for exon 19 deletion and exon 21 (L858R) substitution and found positive for (60%) and (40%) of cases, respectively. Amongst 90 EGFR-negative patients, 4 (4.4%) had the EML4-ALK fusion gene, while 86 (95.5%) were negative for EML4-ALK. This study’s EML4-ALK fusion gene incidence was only (4%). Females have a higher occurrence of EGFR mutations than males (p=0.003) and the frequency of EGFR mutation was higher in non-smokers. The overall incidence of the EML4-ALK fusion gene was (4.44%) and was higher in patients below 60 years of age.

The Personalized Inherited Signature Predisposing to Non-Small-Cell Lung Cancer in Non-Smokers.

Lung cancer (LC) continues to be an important public health problem, being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never-smoker early-onset LC patients, which does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer-predisposing genes in non-smokers patients, giving experimental support to a model of a "private genetic epidemiology". Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib's model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bioinformatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer-predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: (i) downregulation in LC tissue (indicating a "second hit" in tumor suppressor genes); (ii) upregulation in cancer tissue (likely oncogene); and (iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with a functional effect in tumor-predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of the familial clustering of non-small-cell lung cancer. In conclusion, these findings indicate that each patient has his/her own "predisposing signature" to cancer development and suggest the use of personalized therapeutic strategies in lung cancer.

An Artificial Intelligence (AI)-Integrated Approach to Enhance Early Detection and Personalized Treatment Strategies in Lung Cancer Among Smokers: A Literature Review.

Lung cancer (LC) is a significant global health issue, particularly among smokers, and is characterized by high rates of incidence and mortality. This comprehensive review offers detailed insights into the potential of artificial intelligence (AI) to revolutionize early detection and personalized treatment strategies for LC. By critically evaluating the limitations of conventional methodologies, we emphasize the innovative potential of AI-driven risk prediction models and imaging analyses to enhance diagnostic precision and improve patient outcomes. Our in-depth analysis of the current state of AI integration in LC care highlights the achievements and challenges encountered in real-world applications, thereby shedding light on practical implementation. Furthermore, we examined the profound implications of AI on treatment response, survival rates, and patient satisfaction, addressing ethical considerations to ensure responsible deployment. In the future, we will outline emerging technologies, anticipate potential barriers to their adoption, and identify areas for further research, emphasizing the importance of collaborative efforts to fully harness the transformative potential of AI in reshaping LC therapy. Ultimately, this review underscores the transformative impact of AI on LC care and advocates for a collective commitment to innovation, collaboration, and ethical stewardship in healthcare.

Cytosolic DNA sensor AIM2 promotes KRAS-driven lung cancer independent of inflammasomes.

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co-operators of oncogenic KRAS in the lung remains ill-defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent-in-melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS-addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine-derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome-associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK-induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D-driven LAC in both hematopoietic (immune) and non-hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2-deficient mice is associated with unaltered protein levels of mature Caspase-1 and IL-1β inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D-driven LAC. In support of these invivo findings, AIM2, but not mature Caspase-1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor-promoting role, independent of inflammasomes, in mutant KRAS-addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer.

Identification of potential regulatory mechanisms and therapeutic targets for lung cancer

Lung cancer poses a significant health threat globally, especially in regions like India, with 5-year survival rates remain alarmingly low. Our study aimed to uncover key markers for effective treatment and early detection. We identified specific genes related to lung cancer using the BioXpress database and delved into their roles through DAVID enrichment analysis. By employing network theory, we explored the intricate interactions within lung cancer networks, identifying ASPM and MKI67 as crucial regulator genes. Predictions of microRNA and transcription factor interactions provided additional insights. Examining gene expression patterns using GEPIA and KM Plotter revealed the clinical relevance of these key genes. In our pursuit of targeted therapies, Drug Bank pointed to methotrexate as a potential drug for the identified key regulator genes. Confirming this, molecular docking studies through Swiss Dock showed promising binding interactions. To ensure stability, we conducted molecular dynamics simulations using the AMBER 16 suite. In summary, our study pinpoints ASPM and MKI67 as vital regulators in lung cancer networks. The identification of hub genes and functional pathways enhances our understanding of molecular processes, offering potential therapeutic targets. Importantly, methotrexate emerged as a promising drug candidate, supported by robust docking and simulation studies. These findings lay a solid foundation for further experimental validations and hold promise for advancing personalized therapeutic strategies in lung cancer. Communicated by Ramaswamy H. Sarma

Drug resistance mechanism and reversal strategy in lung cancer immunotherapy.

Among all malignant tumors, lung cancer has the highest mortality and morbidity rates. The non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the most common histological subtypes. Although there are a number of internationally recognized lung cancer therapy regimens, their therapeutic effects remain inadequate. The outlook for individuals with lung carcinoma has ameliorated partly thanks to the intensive study of the tumor microenvironment and immune checkpoint inhibitors. Numerous cancers have been effectively treated with immunotherapy, which has had positive therapeutic results. Global clinical trials have validated that PD-1/PD-L1 inhibitors are effective and safe for treating lung cancer either independently or in combination, and they are gradually being recommended as systemic treatment medications by numerous guidelines. However, the immunotherapy resistance restricts the immunotherapy efficacy due to the formation of tumor immunosuppressive microenvironment and tumor mutations, and immunotherapy is only effective for a small percentage of lung cancer patients. To summarize, while tumor immunotherapy is benefiting an increasing number of lung cancer patients, most of them still develop natural or acquired resistance during immunotherapy. Consequently, a crucial and urgent topic is understanding and tackling drug resistance triggered by immunotherapy in lung cancer treatment. This review will outline the presently recognized mechanisms of immunotherapy resistance and reversal strategies in lung cancer.

AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages

Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting "M2-like" phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to interact with endothelial cells and facilitate formation of primitive vascular networks. We also found that AXL-STAT3 inhibition can impede the recruitment of TAMs in a xenograft mouse model, thereby suppressing tumor growth. These findings suggest the potential application of AXL-STAT3-related markers to quantitatively assess metastatic potential and inform therapeutic strategies in lung cancer.

Montelukast Inhibits Lung Cancer Cell Migration by Suppressing Cysteinyl Leukotriene Receptor 1 Expression In vitro.

Lung cancer is a major threat to public health and remains difficult to treat. Repositioning of existing drugs has emerged as a therapeutic strategy in lung cancer. Clinically, low-dose montelukast has been used to treat asthma. We evaluated the potential of using montelukast to treat lung cancer. Migration was detected using wound-healing and Transwell assays, the expression of CysLT1 using western blotting, and subcellular localization of CysLT1 using immunofluorescence. CRISPR/Cas9 technology was used to further investigate the function of CysLT1. Subcellular localization staining showed that the CysLT1 distribution varied in murine and human lung cancer cell lines. Furthermore, montelukast suppressed CysLT1 expression in lung cancer cells. The treated cells also showed weaker migration ability compared with control cells. Knockout of CysLT1 using CRISPR/Cas9 editing in A549 cells further impaired the cell migration ability. Montelukast inhibits the migration of lung cancer cells by suppressing CysLT1 expression, demonstrating the potential of using CysLT1 as a therapeutic target in lung cancer.

Abstract 5302: Unmasking aggressive tumor profiles in lung adenocarcinomas through the molecular abundances and catalytic action of serine hydrolases

Abstract (a) Current proteomic methods quantify solely the catalytically active portion of enzymes without normalizing the active portion to the total enzyme amount, thus compromising comparison of the results. We take advantage of a SWATH/DIA-MS workflow and describe a method based on depletion-dependent ABPP (dd-ABPP) able to concurrently determine catalytically active enzymes and their total molecular abundances, as well as quantify the contextual sample proteomes. (b) We monitored high quality peptides of more than 190 SH activities and molecular abundances of around 4000 contextual tissue proteins in advanced lung adenocarcinomas (LUAD). While we found that LUAD tumors display enhanced proteolytic activities compared with control lung tissue, the most prominent characteristic of an aggressive tumor phenotype was enhanced lipolysis of metabolic SHs emphasized by IAH1, ABHD12, LYPLA2 and ABHD10. (c) Molecular signatures of the activity profiles of 23 SHs and 59 contextual tissue proteins discriminate aggressive tumors at the time of diagnosis. Enhanced detection of S-palmitoylated proteins correlating by active-enzyme capture uncovers their functional links with the metabolic SHs related to lipoprotein depalmitoylation via enzymes displaying increased de-palmitoylase activities and enhanced fatty acid metabolism in aggressive LUAD. To further validate our findings, we analysed LUAD tumors for panels of saturated and unsaturated fatty acid (C8-C22) levels. Strikingly, we detected a statistically significant increase in monounsaturated palmitoleic acid (C16:1) in the aggressive compared with less-aggressive tumors. Notably, the primary source of palmitoleic acid in the cellular environments results from an excess of free palmitic acid and its conversion by rate-limiting enzyme Stearoyl-CoA desaturase 1 (SCD) that is enhanced in LUAD cancer. (d) We detected a significant increase in palmitoleic acid levels in aggressive tumors. To a certain extent our data support previous findings on the active process of lipid desaturation in lung adenocarcinoma cells as the main source of energy for cell proliferation. Our approach also revealed that changes in the active lipase fractions between subtypes do not follow changes in enzyme protein quantities, suggesting that lipase regulations are related rather to peculiarities of the enzyme protein sequence, a distorted enzyme-inhibitor equilibrium, or a distorted molecular composition of the tissue itself. Since the inhibitors of serine lipases are promising targets in other RAS-mutant carcinomas, and the inhibitors of a rate-limiting SCD1 enzyme prevent palmitic acid conversion to a monounsaturated form, these metabolic vulnerabilities detected in aggressive LUAD will be helpful for future therapeutic strategies in lung cancer. Citation Format: Tatjana Sajic, Stephan Arni, Rudolf Aebersold, Sven Hillinger. Unmasking aggressive tumor profiles in lung adenocarcinomas through the molecular abundances and catalytic action of serine hydrolases. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5302.

Pathological response characteristics and surgical outcome following use of emerging neoadjuvant treatment strategies in lung cancer: a narrative review

Pathological response characteristics and surgical outcome following use of emerging neoadjuvant treatment strategies in lung cancer: a narrative review

Network Dynamics Caused by Genomic Alteration Determine the Therapeutic Response to FGFR Inhibitors for Lung Cancer.

Recently, FGFR inhibitors have been highlighted as promising targeted drugs due to the high prevalence of FGFR1 amplification in cancer patients. Although various potential biomarkers for FGFR inhibitors have been suggested, their functional effects have been shown to be limited due to the complexity of the cancer signaling network and the heterogenous genomic conditions of patients. To overcome such limitations, we have reconstructed a lung cancer network model by integrating a cell line genomic database and analyzing the model in order to understand the underlying mechanism of heterogeneous drug responses. Here, we identify novel genomic context-specific candidates that can increase the efficacy of FGFR inhibitors. Furthermore, we suggest optimal targets that can induce more effective therapeutic responses than that of FGFR inhibitors in each of the FGFR-resistant lung cancer cells through computational simulations at a system level. Our findings provide new insights into the regulatory mechanism of differential responses to FGFR inhibitors for optimal therapeutic strategies in lung cancer.

Abstract 1887: Discrimination of aggressive tumor profiles in lung adenocarcinomas using activity based protein profiling by SWATH/DIA-MS mode

Abstract (a) Activity-based proteome profiling (ABPP) probes combined with mass spectrometry (MS) is the tool of functional proteomics for the quantification of catalytically active enzymes. Here, we applied a depletion-dependent ABPP for serine hydrolase (SH) profiling in 30-μm thickness cryosections of optimal-cutting-temperature (OCT)-embedded tissue of advanced lung adenocarcinomas (LUAD). (b) For the proof-of-concept, we profiled SH activities in advanced LUAD disease. We retrospectively analyzed hydrolase activity differences with prognostic values related to aggressive phenotype based on clinical data collected over the course of disease progression. Interestingly, detection of proteins correlating by active-enzyme capture uncover their functional links with the metabolic SHs related to the enhanced palmitoylation-depalmitoylation cycle of lipoproteins in aggressive LUAD. In contrast, the standard DDA-MS analysis of on-bead-depleted enzymes detected 95 SH’s of which less than 60 enzymes were quantified based on spectral counting. (c) We found enhanced activities of dozen SHs in all LUAD tumors. Remarkably, the activity of 11 hydrolases emphasized by IAH1, ABHD12, LYPLA2 and MST1 discriminate aggressive tumors at the time of diagnosis. Functional analysis leveraging enzymes and associated co-depleted proteins revealed catabolic processing of lipoproteins and enrichment of enzymes displaying increased de-palmitoylase activities. This is interesting because multiple isoforms of RAS protein (K-RAS, H-RAS and N-RAS), the most frequently mutated oncogene in human cancers including LUAD (i.e. 30% of LUADs contain somatic K-Ras mutation), attain oncogenic properties only in depalmitoylated state which favor protein intracellular trafficking by detachment from hydrophobic plasma membrane. In line, mutant K-Ras protein co-localize on outer mitochondrion membrane and interact with glycolytic enzymes (hexokinase-1 and -2) only in depalmitoylated state. This interaction induce K-Ras oncogenic properties and increased glucose uptake and glycolysis even in the presence of abundant oxygen (Warburg effect). Curiously, we observed co-depletion of mitochondrial proteins including glycolytic hexokinase 2 with several lipases displaying increase depalmitoylase activity in short LUAD survivals. (d) Surprisingly, an evident disagreement in the activity of enzymes involved in lipolysis and protein depalmitoylation (i.e. IAH1, ABHD12, LYPLA2) was discovered between LUAD survival subtypes. These essential metabolic differences were uncovered by our standard proteomic analysis and to our knowledge have not been reported. Since the inhibitors of serine lipases are promising targets in other RAS-mutant carcinomas, this metabolic vulnerabilities discovered in aggressive LUAD can be explored as promising therapeutic strategies in lung cancer. Citation Format: Tatjana Sajic, Stephan Arni, Rudolf Aebersold, Sven Hillinger. Discrimination of aggressive tumor profiles in lung adenocarcinomas using activity based protein profiling by SWATH/DIA-MS mode [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1887.

Long Noncoding RNAs and Circular RNAs in the Metabolic Reprogramming of Lung Cancer: Functions, Mechanisms, and Clinical Potential.

As key regulators of gene function, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are generally accepted to be involved in lung cancer pathogenesis and progression. Recent research has clarified the phenomenon of metabolic reprogramming in lung cancer because of its significant role in tumor proliferation, migration, invasion, metastasis, and other malignant biological behaviors. Emerging evidence has also shown a relationship between the aberrant expression of lncRNAs and circRNAs and metabolic reprogramming in lung cancer tumorigenesis. This review provides insight regarding the roles of different lncRNAs and circRNAs in lung cancer metabolic reprogramming, by how they target transporter proteins and key enzymes in glucose, lipid, and glutamine metabolic signaling pathways. The clinical potential of lncRNAs and circRNAs as early diagnostic biomarkers and components of therapeutic strategies in lung cancer is further discussed, including current challenges in their utilization from the bench to the bedside and how to adopt a proper delivery system for their therapeutic use.

Syntaxin 18 regulates the DNA damage response and epithelial-to-mesenchymal transition to promote radiation resistance of lung cancer

Radiotherapy is an important modality in lung cancer treatment. Despite advances in treatment planning and dose delivery, patient benefit is still limited by in-field relapse and metastatic recurrence. Simultaneous application of cisplatinum-based chemotherapy leads to moderately improved outcomes, thus providing proof-of-concept for radiosensitization strategies in lung cancer. In an unbiased functional genetic screen for radiosensitization targets in lung cancer, we identified syntaxin 18, a protein involved in retrograde vesicular transport between the Golgi apparatus and endoplasmic reticulum, as mediator of radioresistance. Downregulation of endogenous syntaxin 18 specifically reduced clonogenic survival of radioresistant and radiosensitive lung cancer cells following X-radiation. Gene expression programs regulating DNA repair, mitotic checkpoints and mitosis were altered in isogenic cells with reduced syntaxin 18 expression. Functionally, this translated into impaired DNA damage-induced cell cycle checkpoints leading to cell death by mitotic catastrophe. Interestingly, downregulation of syntaxin 18 in lung cancer cells also impaired expression of markers of epithelial-mesenchymal-transition, and reduced migration and invasion capacity. These findings suggest that syntaxin 18 is a key player regulating genes responsible for controlling the growth of the primary tumor as well as metastases upon radiotherapy of lung cancer. They provide a promising lead for biologically rational radiosensitization strategies impacting on radiation-induced cell death as well as metastasis.

Comprehensive genomic and immune profiling defines immunotherapy treatment in patients with NSCLC with low PD-L1 IHC.

2623 Background: Immune checkpoint inhibitors (ICIs) have emerged as effective treatments in non-small cell lung cancer (NSCLC). While the clinical utility of single agent ICI or in combination with chemotherapy has been well established, there remains an unmet need for the development of biomarkers that can better predict response. To address this need, we developed and applied a combination genomic and immune biomarker strategy to ICI-treated NSCLC patients which identified distinct patient subgroups with differential benefit among single agent or combination ICI treatment strategies. Methods: A discovery cohort (DC) of 5450 tumors across 37 histologies were evaluated by comprehensive genomic and immune profiling of the tumor immune microenvironment. Individual and combination biomarker assessment included PD-L1 IHC, TMB, tumor inflammation (TIGS), cell proliferation (CP) and cancer testis antigen burden (CTAB). From this cohort, combinations of molecular and immune biomarkers were identified and applied to a retrospective cohort (RC) of 225 metastatic NSCLC patients treated with pembrolizumab + chemo or pembrolizumab alone to correlate with response. Comparison of objective response rates (ORR) was performed using Chi-square test. Kaplan-Meir analysis was performed to test for differences in overall survival (OS) and 1-year OS. Results: Unsupervised analysis of the DC revealed four distinct biomarker combination groups that describe underlying tumor immunobiology: tumor dominant (CTAB, TMB, CP High), proliferative (CP High), inflamed (TIGS High), and checkpoint (PDL1, TIGS and TMB High). Application of these biomarker groups to the RC demonstrated significant differences in response to ICI regimens between groups (p = 0.04). Patients in the proliferative group (35.1%, 79/225; median PD-L1 = 20% TPS) treated with single agent pembrolizumab showed a significantly higher ORR (59%; 16/27) compared to pembrolizumab + chemo (27%; 14/52; p = 0.005), significantly improved 1-yr OS (p = 0.03), and trend towards better OS (p = 0.14). Importantly, patients in the inflamed group (16%, 36/225; median PD-L1 = 1% TPS), suggested that pembrolizumab + chemo (ORR 26.1%; 6/23) was not associated with ORR compared to pembrolizumab (ORR 31%; 4/13, p = 0.76), or OS (p = 0.37) and 1-yr OS (p = 0.57). Conclusions: Comprehensive genomic and immune profiling may identify PD-L1 low NSCLC patients who benefit from single agent pembrolizumab. PD-L1 low NSCLC patients with a proliferative phenotype may benefit from single agent pembrolizumab, whereas PD-L1 low cases with an inflamed phenotype may benefit from both single agent and combination pembrolizumab. Although further clinical validation of these predictive biomarker combinations is required, this data-driven approach demonstrates the potential to provide treatment decision support when selecting an ICI therapeutic strategy in lung cancer.

Deletion of TRIB3 disrupts the tumor progression induced by integrin \u03b1v\u03b23 in lung cancer

BackgroundIntegrin αvβ3 has been proposed as crucial determinant for tumor sustained progression and a molecular marker for the estimation of tumor angiogenesis. Our study suggested that integrin αvβ3 could efficiently promote lung cancer cell proliferation and stem-like phenotypes in a tribbles homolog 3 (TRIB3) dependent manner.ResultIntegrin αvβ3 could mediate the activation of FAK/AKT pro-survival signaling pathway. Meanwhile, activated TRIB3 interacted with AKT to upregulated FOXO1 and SOX2 expression, resulting in sustained tumor progression in lung cancer. Our further analysis revealed that TRIB3 was significantly upregulated in lung tumor tissues and correlated with the poor outcome in clinical patients, indicating the potential role of TRIB3 in diagnostic and prognostic estimation for patients with lung cancer.ConclusionOur study showed here for the first time that integrin αvβ3 promote lung cancer development by activating the FAK/AKT/SOX2 axis in a TRIB3 dependent signaling pathway, and interrupting TRIB3/AKT interaction significantly improved the outcome of chemotherapy in tumor-bearing mice, representing a promising therapeutic strategy in lung cancer.

Prognostic Value of Pretreatment Geriatric Nutrition Risk Index in Lung Cancer Patients: A Meta-Analysis

Purpose To explore the prognostic value of pretreatment Geriatric Nutrition Risk Index (GNRI) in lung cancer patients. Methods The PubMed, EMBASE and Web of Science electronic databases were searched up to October 5, 2021 for relevant studies. The primary and second outcomes were the overall survival (OS) and progression-free survival (PFS) and the hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association between GNRI and prognosis of lung cancer patients. Results A total of eight retrospective studies involving 2012 patients were included and all of them were from Asian countries. The pooled results demonstrated that lower pretreatment GNRI was significantly associated with poor OS (HR = 2.01, 95% CI: 1.68–2.42, P < 0.001) and PFS (HR = 1.50, 95% CI: 1.24–1.81, P < 0.001). Subgroup analysis based on the treatment (surgery vs non-surgery) and tumor type (non-small cell lung cancer vs small cell lung cancer) showed similar results. Conclusion Lower pretreatment GNRI was an independent prognostic risk factor for lung cancer patients and might contribute to the evaluation of prognosis and formulation of therapy strategies in lung cancer.

Targeting KDM4C enhances CD8+ T cell mediated antitumor immunity by activating chemokine CXCL10 transcription in lung cancer

BackgroundAlthough immune checkpoint blockade (ICB) has been proven to achieve a persistent therapeutic response in various tumor types, only 20%–40% of patients benefit from this treatment. Radiotherapy (RT) can enhance...

Ferroptosis and Its Potential Role in Lung Cancer: Updated Evidence from Pathogenesis to Therapy.

Lung cancer is characterized by high morbidity and mortality rates, and its occurrence is associated with many types of cell death. As a new form of regulated cell death, ferroptosis is an iron- dependent pattern of cell death and characterized by lethal accumulation of lipid-based reactive oxygen species (ROS), which is different from apoptosis, necrosis and autophagy at both the morphological and biochemical levels. It plays an important role in the development of lung cancer and induction of ferroptosis in lung cancer cells has become a new strategy for anti- lung cancer treatment. However, a few reviews summarized ferroptosis and its role in lung cancer has not been elucidated, and the precise mechanism of ferroptosis modeling lung cancer has not yet been revealed till date. Herein, we review the latest literature on the process of ferroptosis regarding lung cancer, including basic molecular or biology mechanistic studies both in vivo and in vitro, as well as human studies with a more translational or clinical approach. This review provides a practical, concise and updated outline on the mechanisms and therapeutic strategies in lung cancer with ferroptosis alterations. Looking ahead, further studies are required to uncover the possible modulatory relationship between ferroptosis and lung cancer.

Identification of a Rare EGFR T790I Mutation in Lung Adenocarcinoma Sensitive to Osimertinib.

Estimated glomerular filtration rate (EGFR)-sensitive mutations are extremely important for targeted treatment strategies in lung cancer. Osimertinib can effectively inhibit the activity of EGFR-sensitive mutations, including the T790M mutation. However, the efficiency of osimertinib for rare mutation types of T790 is unclear. Here, we report the case of a Chinese patient with lung adenocarcinoma (LADC) harboring a T790I mutation who achieved significant benefits from osimertinib treatment.