Quercetagitrin targets EIF3D to activate NCOA4-mediated ferritinophagy-dependent ferroptosis for the treatment of non-small cell lung cancer.

Real-world comparative effectiveness of atezolizumab versus durvalumab for extensive-stage small-cell lung cancer.

Semi-rigid linkers improve the pharmacokinetic properties and therapeutic efficacy of BET PROTACs for cancer therapy.

Fufang Banmao Capsule (FBC) is clinically applied in the treatment of non-small cell lung cancer (NSCLC), yet its underlying pharmacological mechanism remains to be fully elucidated. This study aimed to systematically elucidate the pharmacological actions of FBC against NSCLC by integrating network pharmacology and Mendelian randomization approaches. Active components and potential targets of FBC were retrieved from the BATMAN-TCM database, while NSCLC-related therapeutic targets were collected from OMIM, TTD, and DisGeNet. Enrichment analysis and a "Herbs-Ingredients-Targets-Pathways" network were constructed. Core targets were further identified through protein-protein interaction and Mendelian randomization analyses, followed by colocaliza tion tests and molecular docking validation. A total of 152 potential FBC targets for NSCLC were identified, with seven candidates shortlisted. Among these, TNF and PIK3CA emerged as key protective targets (P<0.0025, OR<1). Colocalization analysis suggested possible shared genetic causality of TNF and PIK3CA single nucleotide polymorphisms with increased NSCLC risk. Molecular docking confirmed strong binding interactions between these targets and active FBC compounds such as resveratrol. The findings provide a theoretical foundation and new research directions for further investigation into the anti-NSCLC mechanism of FBC, supporting future innovation in therapeutic strategies.

Lung cancer remains a leading cause of global cancer mortality, with therapeutic efficacy significantly hampered by intrinsic and acquired therapy resistance. Solute carrier (SLC) and ATP-binding cassette (ABC) transporters have emerged as pivotal regulators orchestrating the transmembrane transport of diverse substrates to critically influence lung cancer progression and treatment response. This review systematically examines the pathophysiological roles of key transporters in lung cancer progression and therapeutic response, with a particular emphasis on their functions in mediating crosstalk within the tumor microenvironment (TME). It assesses the current knowledge in this field, elucidates the underlying molecular mechanisms, and highlights potential avenues for future research and clinical translation. SLC and ABC transporters critically contribute to the aggressiveness of lung cancer by orchestrating multiple facets of its malignant phenotype. This encompasses promoting cell proliferation, suppressing cell death, facilitating tumor invasion and metastasis, sustaining cancer stem cell (CSC) self-renewal, and modulating chemotherapy sensitivity and resistance. Furthermore, they mediate immunosuppression within the TME through dynamic crosstalk with resident stromal and immune cells. Thus, the substantial involvement of SLC and ABC transporters in lung cancer pathogenesis and therapeutic resistance definitively positions them as pivotal molecular vulnerabilities and actionable targets for developing novel therapeutic strategies to overcome drug resistance and improve clinical outcomes.

Safety evaluation of tarlatamab: A pharmacovigilance study based on the FAERS database.

Multidrug resistance (MDR) severely limits the efficacy of non-small lung cancer (NSCLC) treatment. Counteracting MDR is very difficult but highly necessary to extend the survival of MDR patients. This work aimed at establishing MDR NSCLC cellular models, to identify mechanisms responsible for their resistance to several treatments and new collateral sensitivity approaches to overcome MDR. Two paclitaxel resistant cell sublines (A549-CDR1 and A549-CDR2) were established, by treating A549 cells with increasing concentrations of paclitaxel. The proteomic profile (liquid chromatography-mass spectrometry) of these sublines was assessed as well as their MDR phenotype by evaluating response to several chemotherapeutic drugs (Sulforhodamine B assay) and the expression levels (Western Blotting) and activity (Rhodamine-123 accumulation assay) of ATP-binding cassette (ABC) transporter proteins. Cell death, reactive oxygen species (ROS) production (flow cytometry) and DNA damage levels (Comet assay and Western Blotting) were also evaluated prior to and following treatments with several drugs. The two established paclitaxel resistant cell sublines exhibited distinct proteomic profiles, although both presented a MDR phenotype, confirmed by cross-resistance to other chemotherapeutic drugs and increased expression levels and activity of ABC transporter proteins. They presented lower proliferation, higher ROS levels and increased DNA damage levels. These MDR cells were more sensitive than their parental cells to DNA damaging drugs that are not P-glycoprotein (P-gp) substrates, thus presenting collateral sensitivity to such drugs. The established NSCLC MDR cell lines are promising models to understanding mechanisms associated with MDR and exploiting collateral sensitivity approaches to overcome MDR in NSCLC.

The effect of frailty on early postoperative outcomes of lobectomy for lung cancer in older adults - A United States National Retrospective Cohort Study.

Novel hydrazone-derived pyrazole-benzofuran compounds inhibit cancer cell growth by targeting MMPs, caspases, and PI3K/AKT/mTOR signaling pathway.

Xbp1-driven lipid metabolism promotes immunosuppression in lung cancer: Jianpi Chutan Jiedu formula reshapes metabolic-immune crosstalk.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and seriously threatens the lives of many people worldwide. The difficulty in early diagnosis of lung cancer has always been a difficulty in lung cancer treatment, and basic leucine zipper nuclear factor 1 (BLZF1) has been shown to promote the occurrence and development of various cancers. This study used 505 LUAD patients in TCGA (TCGA dataset) and 60 LUAD patients in Yunnan Cancer Hospital (Clinical dataset) as research subjects to explore the role of BLZF1 in LUAD. The study found that the expression levels of mRNA and protein of the BLZF1 gene in cancer tissues were significantly higher than those in para-cancer tissues in the TCGA dataset and clinical dataset (P < 0.001). Receiver operating characteristic (ROC) curves analysis found that the AUC value of BLZF1 was 0.759 (95% CI = 0.7049-0.8140, P < 0.0001) in the TCGA dataset, and the AUC value was 0.9985 (95% CI = 0.9954-1.0000, P < 0.0001) in the clinical dataset. Moreover, the BLZF1 gene expression level in the two data sets was significantly correlated with the patient's T stage, and survival analysis showed that high BLZF1 gene expression levels were associated with decreased recurrence-free survival (RFS) (HR = 1.510, 95% Cl = 1.095-2.083, P = 0.012) and overall survival (OS) (HR = 1.472, 95% Cl = 1.099-1.973, P = 0.010). Protein-protein interaction (PPI) and enrichment analysis showed that the BLZF1 gene was closely associated with biological processes such as Golgi function, vesicle transport and cell membrane system maintenance. The expression correlation of BLZF1 with glycolysis-related genes indicated that BLZF1 may play a role in LUAD by participating in the sugar metabolism pathway. In addition, this study downregulated the expression of BLZF1 by small interfering RNA (si-BLZF1), and downregulation of BLZF1 expression significantly inhibited the proliferation, cloning, migration and invasion of LUAD cells. Therefore, BLZF1 may be involved in the occurrence and development of lung adenocarcinoma, which can be a potential diagnostic biomarker in clinical practice.

Resistance to Osimertinib via the EGFR C797S mutation is a major challenge in the treatment of nonsmall cell lung cancer (NSCLC). Combining Osimertinib with SG-55, a novel selective AKR1C3 inhibitor, effectively reverses this resistance, restoring sensitivity in NSCLC cells with the C797S mutation. This highlights AKR1C3 inhibition in overcoming antitumor drug resistance for further preclinical investigation.

Intensity-modulated proton therapy (IMPT) provides steep dose gradients but is vulnerable to range uncertainties and respiratory motion, leading to interplay effects in lung cancer radiotherapy. This study aimed to develop a deep learning-based 4D optimization framework to mitigate these challenges. The proposed workflow integrates a deep learning-based 4D optimization framework combining dose prediction on 4DCTs, water-equivalent thickness variation-guided beam selection (ΔWET-guided beam selection), and dose mimicking to generate 4D-robust IMPT plans..&#xD;Approach: The planning process uses a U-Net model to predict robust dose distributions based on multiple CT inputs, followed by dose mimicking for plan generation. In this study, data from 62 patients with lung cancer, including 4DCT were used, with dose data generated from the beam angles which were selected based on the ΔWET at different phases. The dataset was split into 42 training, 10 validation, and 10 testing cases. The dose volume histogram and robustness of the plans were evaluated.&#xD;Main results: We demonstrated that deep learning-based 4D (DL4D) plans maintained target coverage across respiratory phases and improved conformity over the robust plans produced by the internal gross tumor volume-override (IGTV-override) CT. The conformity index (CI) was higher for DL4D plans both for the IGTV on IGTV-override CT (80.8% vs. 69.4%, p = 0.002) and for the GTV in dose accumulation (62.5% vs. 55.5%, p = 0.002). Accumulated D98% of the GTV was close to the prescription dose for both (70.3 Gy vs. 71.5. Gy, p = 0.131). OAR doses were clinically comparable. &#xD;Significance: Deep learning-based 4D optimization with ΔWET-guided beam selection and dose mimicking yields IMPT plans with better conformity, offering an efficient alternative to conventional 4D robust optimization for lung cancer treatment plans.

A review on nanostructured chitosan platforms for controlled and targeted delivery of paclitaxel in lung cancer treatment.

Translated article] Real-world effectiveness and safety of atezolizumab-carboplatin-etoposide regimen in extensive-stage small-cell lung cancer.

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 axis have revolutionized metastatic non-small cell lung cancer (mNSCLC) treatment. However, disease progression remains a concern, and the role of the complex tumor microenvironment (TME) in treatment failure is not fully understood. In this biomarker study involving 103 patients with mNSCLC-including 81 patients who received ICI treatment-we evaluated the association between heterogeneous immune cell subsets and ICI efficacy through single-cell spatial profiling of pretreatment tumor tissue, using a 29-marker multiplex immunohistochemistry platform built for in-depth dissection of the TME. Among various types of intratumoral lymphocytes including T-helper 1 cells, regulatory T cells, and natural killer cells, only CD8+ T cells (TILs) were associated with ICI efficacy. Computational tissue segmentation underscored the importance of direct physical interactions between CD8+ TILs and cancer cells for ICI efficacy. TIL phenotyping identified CD39/CD103/Ki-67 positivity as a hallmark of exhausted yet functional tumor-reactive CD8+ TILs. Immunosuppressive tumor-associated macrophages (TAMs) and cancer-associated fibroblasts were independent unfavorable adversaries. High CD73 expression on cancer cells was suggested to confer tolerance to ICI in EGFR/ALK-oncogene+ NSCLC, potentially through M2-TAM accumulation and aberrant angiogenesis. Our study delineates the clinical relevance of heterogeneous immune cell subsets in ICI-treated mNSCLC, aiding the development of targeted therapeutic strategies. Not applicable because this is a retrospective study. Osaka Cancer Society, KANAE Foundation for the Promotion of Medical Science, SGH Foundation, and YOKOYAMA Foundation for Clinical Pharmacology.

Radiotherapy is the central component in non-small cell lung cancer (NSCLC) treatment. Nonetheless, its therapeutic effectiveness is frequently compromised by adaptive engagement of prosurvival signaling pathways that foster radioresistance. STAT3 functions as the central signaling node that orchestrates cellular survival responses following radiation exposure. This study investigated whether nitroxoline, a clinically approved antimicrobial agent with STAT3-inhibitory activity, enhances radiosensitivity of NSCLC cells and how these effects are mechanistically regulated. We examined the combined effects of nitroxoline and radiation on cell viability and associated signaling pathways in NSCLC cells. Nitroxoline significantly enhanced radiation-induced cytotoxicity and suppressed clonogenic survival compared with radiation alone. Irradiation increased STAT3, AKT, and mTOR phosphorylation, whereas nitroxoline effectively suppressed the basal and radiation-induced activation of these pathways. The combination treatment markedly augmented radiation-induced apoptosis, as demonstrated by increased p53 expression and enhanced PARP and caspase-3 cleavage. Additionally, nitroxoline amplified radiation-induced DNA damage signaling, resulting in pronounced γ-H2AX and DNA-PKcs accumulation. Nitroxoline enhanced NSCLC cell radiosensitivity by suppressing STAT3-AKT-mTOR survival signaling, promoting apoptosis, and amplifying radiation-induced DNA damage, indicating the potential of repurposing nitroxoline as a radiosensitizer to improve radiotherapy outcomes in patients with NSCLC.

Lung cancer has one of the highest death rates of all cancers. It is a serious health risk that must be addressed. Non-small cell lung cancer makes up 85% of lung cancer cases, which should be the main focus of treatments. But even with new approaches like immune checkpoint inhibition, the treatment works for only a small group of patients. This review discusses the biological foundations of lung cancer immunotherapy, the function of immune checkpoint inhibitors (ICIs), and the unpredictable nature of the lung tumor microenvironment. The paper then evaluates the use of ICIs, possible combination therapies, and major limitations currently faced in the field. These limitations include resistance mechanisms, immune-related side effects, and tumor heterogeneity. New strategies, such as biomarker-guided immunotherapy, novel immune treatments, and technologies that support the field, are also evaluated and discussed as possible solutions. In the end, evidence has shown the impact and influence of immunotherapy in cancer treatment. Future progress in lung cancer immunotherapy will depend on precision treatment strategies, combination approaches, and new immune therapies to lay a foundation for sustained, consistent clinical outcomes.

Multi-omics analysis reveals Yishen Qutong formula promotes ferroptosis in Lewis lung cancer associated with Keap1/Nrf2/Nqo1 pathway modulation.

Design, synthesis, and biological evaluation of a hydrophilic 20-O-glycyl ester prodrug of 10-methoxycamptothecin against lung cancer.